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8      PERIODICALS 
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WORKS  NOT  INCLUDED  IN  THESE 
VOLUMES 

Physiology  of  Man — Five  Volumes  of 
about  500  pages  each,  1866-1874.  Second 
Edition,  1875.  Volumes  IV  and  V  are  out 
of  print. 

Manual  of  Chemical  Examination 
OF  THE  Urine  in  Disease,  pp.  76,  1870. 
Sixth  Edition,  1884. 

Text -Book  of  Human  Physiology, 
pp.  978,  187 1.     Fourth  Edition,  1888. 


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i/frnton  (T^^iJidr 


COLLECTED  ESSAYS 
AND  ARTICLES  ON 
PHYSIOLOGY  AND  MEDICINE 

BY 

AUSTIN    FLINT.   MD..    LL.  D. 

PROFESSOR    OF    PHYSIOLOGY    IX     THE    CORNELL    UNIVERSITY    MEDICAL    COLLEGE  ;     COXSULTIXG 
PHYSICIAN-    TO    BELLEVfE    HOSPITAL  ;     CONSILTING    PHYSICIAN    TO     THE    JIANHATTAN    STATE 
HOSPITAL   FOR    THE   INSANE   ANT)    PRESIDENT   OF  THE   CONSULTING  BOARD  ;   MEMBER  OF  THE 
A-MERICAN   MEDICAL   ASSOCIATION"  :    FELLOW   OF  THE    NEW  YORK  STATE  MEDICAL  ASSOCIA- 
TION ;   MEMBER    OF   THE  NEW    YORK    COUNTY   MEDICAL    ASSOCIATION  ;    MEMBER    OF  THE 
MEDICAL  ASSOCIATION  OF  THE    GREATER  CITY    OF   NEW  YORK  ;    HONORARY   MEMBER  OF 
THE  AMERICAN  ACADEMY  OF  MEDICINE  ;    MEMBER  OF  THE  AMERICAN  MEDICO-PSYCHO- 
LOGICAL ASSOCIATION  ;  MEMBER  OF  THE  AMERICAN  PHILOSOPHICAL  SOCIETY  ;   HON- 
ORARY MEMBER  OF  THE  ASSOCIATION  OF  MILITARY  SURGEONS  OF  THE  U.  S.  ;   COR- 
RESPONDEINT  OF   THE  ACADEMY  OF   NATURAL  SCIENCES.  PHILADELPHIA;    FEL- 
LOW OF  THE  AMERia\N   ASSOCIATION    FOR  THE  ADVANCEMENT  OF  SCIENCE  ; 
MEMBER  OF  THE  AMERICAN  ANTHROPOLOGICAL  ASSOCIATION  ;  MEMBER  OF 
THE  AMERICAN  ACADEMY  OF  POLITICAL  AND   SOCIAL  SCIENCE  ;    MEMBER 
OF  THE   EXECUTIVE   CO^LMITTEE  OF  THE   NEW  YORK  PRISON  ASSOCIA- 
TION ;    DECORATION    OF   THE    THIRD    CLASS,    ORDER    OF    THE    BUST 
OF   THE    LIBERATi>R    (B0LIVAR\    REPUBLIC    OF    VEN"EZUELA,  ETC. 

EDITOR    OF    THE    BUFFALO    MEDICAL    JOURNAL,    iSfS-'fo  ;    VISITING    SITSGEON   TO    THE    BUFFALO 

GENERAL   HOSPITAL,    lS58-"53  ;    MEMBER   OF    THE    ERIE   CdU"NTY"    MEDICAL    SOCIETT,  iSjS-'sg  ; 

PR.-FESSOR  OF  PHYSI  'L'lGY  IN  THE  MEDICAL  DEPARTMENT  OF  THE  UNIVERSITY  OF  BUFFALO, 

i858-'5i)  ;   prl>fess<ir  of  physi  >l  iqy  in  the  new  Y'>rk  medical  C'Llege,  i85o-"6o; 

PROFESSOR    of    PHYSIOLOGY    IN    THE     NE^V    ORLEANS    SCHOOL    OF    MEDICINE,     l86o-I6l  ; 
ONE  OF  THE  FOUNDERS  AND    PR  'FESSOR   OF    PHYSIOLOGY  IN   THE  BELLEVUE  HOSPITAL 
MEDICAL    COLLEGE,    l86l-"p8  ;     PROFESSOR    OF    PHi-SIOLOGY    IN    THE    LONG    ISLAND 
C<  'LLEGE  HOSPITAL,  l862-'63  ;   ACTING  ASSISTANT  SURGE'N,  U.  S.  A.,  U.  S.  GENERAL 
HOSPITAL,  CITY  op  NEW  V    RK.   lS52-'65  I   CONSULTING  PHYSICLVN  TO  THE  CLASS 
OF  NERVOUS   DISEASES,  BELLEVUE  HOSPITAL  DISPENSARY,  l866-'74  AND  1887- 
'q6  ;    VISITING  PHYSICIAN  TO  BELLEVUE   HOSPITAL,   lS6o-'74    AND    iSSj-'oP  ; 
SU"RGE    N-GENERAL,    STATE    OF    NEW   YORK,     lS74-'78  '.     EXAMINING   PHY- 
SICIAN, CONNECTICIT   MUTUAL    LIFE    INSURANCE   COMPANY.  NEW   YORK 
OFFICE,  i87I-'8d  ;      PRESIDENT    <'F    THE    NEW   YORK   STATE    MEDICAL 
ASSOCIATION,  1805  ;    VISITING    PHYSICIAN  Ti''  THE  INSANE  PAVILION, 
BELLEVUE    HOSPITAL,    lSa6-"o7  ;     PRESIDENT    OF     THE      JIEDIOVL 
ASSOCIATION    OF    THE    GREATER    CITY    OF     N"EW     YORK,      18Q9. 


N'OLL'ME   FIRST 


NEW    YORK 
D.     AP  PL  ETON    AND     COMPANY 


Copyright,  1903 
By  AUSTIN    FLINT 


QTG 


PREFACE 


After  nearly  a  half-centiiry  of  somewhat  active  and 
varied  literary  work,  I  have  collected  and  printed  what  is 
contained  in  these  two  volumes,  as  an  offering  to  those  to 
whom  I  am  bound  by  ties  of  relationship  or  friendship.  In 
effect,  I  have  omitted  no  article  that  has  been  published 
under  my  name,  however  much  it  may  have  seemed  to  me 
out  of  place  in  a  collection  made  up  chiefly  of  serious  es- 
says on  professional  topics.  This  collection  begins,  indeed, 
with  a  paper  written  in  1855,  and  it  includes  a  few  articles 
published  in  a  periodical  for  young  people.  It  contains, 
therefore,  everything  I  have  written  for  publication  and 
signed,  with  the  exception  of  one  signed  review,  one  or 
two  biographical  memoirs  and  a  very  few  short  articles 
relating  to  professional  controversies  which  happily  have 
long  since  disappeared.  It  does  not  include,  however,  the 
"  Physiology  of  Man,"  in  five  volumes,  "  Text-Book  of 
Human  Physiology  "  and  "  Manual  of  Chemical  Exami- 
nation of  the  Urine  in  Disease." 

I  trust  that  it  may  not  appear  to  those  for  whom 
these  volumes  are  intended,  that  it  would  have  been  bet- 
ter if  I  had  deferred  their  publication  and  left  it  to  be 
done  by  others,  if  at  all.  With  no  intention  or  desire  to 
deprecate  criticism,  I  simply  say  that  they  could  not  have 
appeared  in  their  present  form  unless  the  collection,  ar- 
rangement and  revision  had  been  made  by  myself;  and  I 
feel  that  the  burden  of  publication  should  be  borne  by 
me  and  not  left  as  a  legacy. 


iv  PREFACE 

I  have  revised  all  the  articles  very  carefully,  but  not 
more  freely  than  is  frequently  clone  in  the  correction  of 
first  proofs.  While  I  have  eliminated  some  verbal  redun- 
dancies and  attempted  to  correct  what  seemed  to  me  no- 
ticeable inelegancies  of  expression,  especially  in  the  earlier 
writings,  I  have  not  changed  the  sense  of  any  one  article, 
paragraph  or  sentence.  It  is  proper  that  I  should  make 
this  statement  for  the  reason  that  in  a  short  analysis  of 
some  of  the  articles,  which  is  to  follow,  there  will  be  in- 
volved questions  of  priority  of  experiment,  observation 
and  publication. 

It  was  my  intention  to  arrange  the  articles  chrono- 
logically; but  I  have  deviated  from  this  order  in  putting 
together  those  on  purely  physiological  and  medical  sub- 
jects, following  them  with  the  miscellaneous  writings.  I 
have  also  grouped  a  few  articles  on  similar  topics,  espe- 
cially when  they  represented  series  of  experiments  or  ob- 
servations. In  some  few  instances  there  have  been  partial 
repetitions,  the  same  facts  or  arguments  being  used  in 
different  relations.  With  these  exceptions  the  chrono- 
logical order  has  been  preserved;  and  the  date  and  place 
of  publication  have  been  given  in  every  instance,  so  that 
a  claim  of  priority  of  publication  may  be  verified  by  any 
one  interested  sufficiently  to  refer  to  the  original. 

The  text-books  on  physiology  of  fifty  years  ago  were 
not  often  the  work  of  practical  physiologists;  and  in  at- 
tempts to  present  fairly  the  best  opinions  on  the  questions 
considered,  not  infrequently  opposite  views  of  observers 
were  given,  leaving  to  the  reader  the  responsibility  of 
selection.  It  was  seldom,  indeed,  especially  in  works  pub- 
lished in  the  English  language,  that  matters  in  doubt  or 
dispute  were  discussed  by  authors  practically  familiar  with 
methods  of  physiological  experimentation. 

In  1857,  the  date  of  publication  of  the  article  on  "  Phe- 
nomena of  the  Capillary  Circulation,"  there  were  writers 


PREFACE  V 

of  authority  who  taught  that  the  blood  moved  in  the 
capillary  vessels  in  obedience  to  what  was  called  the 
"  capillary  power,"  an  attractive  force  exerted  by  the  tis- 
sues on  the  nutritive  constituents  of  the  circulating  fluid. 
In  my  inaugural  thesis  (1857)  I  attempted  to  describe  the 
varied  phenomena  observed  in  studying  the  capillary  cir- 
culation under  the  microscope.  In  the  course  of  these 
observations  I  was  fortunate  enough  to  hit  upon  a  method 
of  suppressing  cutaneous  respiration  in  the  frog  by  cover- 
ing the  surface  with  a  coating  of  collodion,  which  enabled 
me  to  study  the  immediate  effects  of  asphyxia  on  the  capil- 
lary circulation  by  direct  examination.  These  were  the 
first  microscopical  observations  of  the  arrest  of  capillary 
circulation  following  suppression  of  the  respiratory  func- 
tion; and  they  seem  to  me  to  be  important  even  now,  as 
showing  that  blood  deficient  in  oxygen  can  not  circulate 
freely  in  the  capillaries,  the  obstruction  being  in  the  sys- 
temic vessels  and  not  in  the  lungs.  While  the  demon- 
stration was  original,  the  theory  was  not  new.  Dr.  John 
Reid,  of  Edinburgh,  advanced  the  same  view  in  1841.  He 
showed  that  the  arterial  blood-pressure  in  an  asphyxiated 
dog  was  much  increased,  while  the  pressure  in  a  corre- 
sponding vein  was  proportionally  diminished  as  the  as- 
phyxia proceeded  to  the  stage  of  insensibihty. 

In  1 861  I  made  a  number  of  experiments  on  the  roots 
of  the  spinal  nerves  and  confirmed  the  observations  of 
Magendie,  made  in  1839,  in  which  it  was  shown  that  the 
anterior  roots  possessed  a  slight  sensibility  derived  from 
recurrent  fibres  from  the  posterior  roots,  concerning 
which  there  had  been  differences  of  opinion.  These  were 
the  first  observations  of  the  kind  made  in  this  country. 

In  1868  I  had  an  opportunity  of  examining  what  pur- 
ported to  be  an  exact  reprint  of  the  celebrated  "  Idea  of 
a  New  Anatomv  of  the  Brain,"  bv  Sir  Charles  Bell,  the 


vi  PREFACE 

then  reputed  discoverer  of  the  distinct  properties  and 
functions  of  the  two  roots  of  the  spinal  nerves.  This 
pamphlet  was,  printed  for  private  distribution  only  and 
w^as  practically  inaccessible.  I  published  in  that  year  an 
extended  review  of  the  claims  of  Bell  and  of  Map^endie  to 
this  important  discovery  and  corrected  an  error  almost 
universal  in  the  literature,  including,  even,  the  works  of 
French  authors,  attributing  the  discovery  to  Bell.  I  make 
mention  here  of  this  publication  for  the  reason  that  it  led 
writers  generally,  for  the  first  time,  to  do  justice  to  the 
claims  of  Magendie.  The  article  was  followed  by  a  re- 
publication of  Sir  Charles  Bell's  pamphlet  in  the  ''  Journal 
of  Physiology,"  in  1869;  and  I  had  the  satisfaction  of  see- 
ing that  the  reprint  W'hich  I  had  used  was  accurate  and 
that  my  conclusions  were  justified. 

In  the  articles  on  the  action  of  the  heart  and  on  respi- 
ration, published  in  1861,  1874,  1877  and  1880,  are  records 
of  experiments  which  justify  a  claim  of  priority  in  the 
description  and  explanation  of  certain  phenomena  ob- 
served later  by  others  and  now  universally  adopted  by 
writers  on  physiology.  I  had  an  opportunity,  while  teach- 
ing physiology  in  the  New  Orleans  School  of  Medicine, 
in  i860  and  1861,  to  experiment  on  alligators  of  large 
size.  It  is  well  known  that  the  excised  heart  of  cold- 
blooded animals  will  continue  to  beat  for  a  considerable 
time.  I  demonstrated  that  the  heart,  when  filled  with 
blood,  the  valves  between  the  cavities  having  been  cut 
away,  wilj  beat  powerfully  and  w'ith  regular  rhythm;  w^hile 
the  pulsations  are  more  rapid,  feeble  and  irregular  w^hen 
the  cavities  are  empty.  I  also  showed  that  the  pulsations 
are  relatively  rapid  and  feeble  when  the  cavities  are  filled 
with  water  instead  of  blood.  I  made  an  application  of 
the  phenomena  observed  to  the  rapid  and  feeble  action 
of  the  heart  in  the  reaction  from  hemorrhage  and  in  ane- 
mia.    The  recent  "  perfusion  experiments,"  made  chiefly 


PREFACE 


vu 


on  the  heart  of  the  frog,  are  to  a  certain  extent  elabora- 
tions of  these  observations.  Systematic  perfusion  experi- 
ments are  said  to  have  been  begun  by  Merunowicz,  in 
Ludwig's  laboratory,  in  1875.  They  were  repeated,  with 
improved  methods,  by  Cyon  and  the  phenomena  observed 
are  now-  the  subject  of  extended  investigation. 

In  this  series  of  experiments  I  showed  that  while  cu- 
rara  usually  paralyzes  the  inhibitory  nerves  of  the  heart, 
as  well  as  the  general  motor  system,  in  alligators  these 
nerves  are  not  affected  by  the  poison.  Bernard  had  shown 
this  to  be  the  case  in  birds.  In  addition  to  the  observa- 
tions on  alligators  I  showed  that  in  dogs  enfeebled  by 
loss  of  blood  inhibition  of  the  heart  is  but  slightly  affected 
by  curara.  I  reasoned  from  this  that  these  nerves  are 
"  protected  from  disturbing  influences,  like  the  action  of 
poisons,  to  a  greater  degree  than  others." 

The  experiments  on  respiration,  published  in  1861,  led 
me  to  think  that  the  "  respiratory  sense  "  had  its  origin 
in  the  general  system  and  was  due  to  want  of  oxygen.  I 
expressed  the  same  opinion  in  an  address  on  the  "  ^lech- 
anism  of  Reflex  Nervous  Action  in  Normal  Respiration," 
published  in  1874. 

In  1877,  when  I  extended  my  observations  on  the 
"  respiratory  sense,"  or  the  starting  point  of  the  impulses 
which  give  rise  to  the  movements  of  inspiration,  opinions 
as  to  the  action  of  the  respiratory  centre  in  the  bulb  were 
varied  and  conflicting.  Rosenthal  (1862)  and  Pfliiger 
(1868),  subsequently  to  my  experiments  of  1861,  had 
shown  that  the  respiratory  sense  was  due  to  a  general 
deficiency  of  oxygen  in  the  system,  having  noted  dyspnea 
in  animals  made  to  breathe  pure  nitrogen  or  hydrogen. 
Kussmaul  and  Tenner  (before  1858),  having  noted  dys- 
pnea after  ligation  of  the  carotids,  extended  previous  ob- 
servations and  referred  the  convulsions  observed  in  suffo- 
cation and  after  profuse  hemorrhage  to  a  deficiency  in 
oxygen  in  the  brain  and  in  the  bulb.     They  described  the 


viii  PREFACE 

so-called  "convulsions  of  anemia";  and  some  physiolo- 
gists assumed  the  existence  of  a  "  convulsion-centre  "  in 
the  bulb.  As  early  as  1839  John  Reid  wrote  that  the 
respiratory  movements  were  due  to  the  action  of  black 
blood  in  the  bulb.  In  1841  Volkmann  attributed  the  re- 
spiratory movements  to  the  stimulation  of  carbonic  acid 
in  every  part  of  the  body.  Direct  and  conclusive  experi- 
ments, however,  showing  the  efifects  of  cutting  off  the 
blood-supply  from  the  brain  and  bulb,-  contrasted  with 
those  observed  after  cutting  ofT  the  supply  from  the  trunk 
and  lower  extremities,  were  wanting.  In  my  experiments, 
first  published  in  1877,  and  discussed  fully,  with  a  review 
of  the  literature,  in  an  article  entitled  "  Is  the  Action  of 
the  Medulla  Oblongata  in  Normal  Respiration  Reflex?  " 
published  in  1880,  I  showed  that  after  arresting  the  respira- 
tory movements  in  animals  by  supplying  air  in  abundance 
to  the  lungs  in  artificial  respiration,  respiratory  efforts 
began,  although  artificial  respiration  was  continued,  when 
the  vessels  given  ofif  from  the  arch  of  the  aorta  were 
tied;  and  that  no  respiratory  efforts  were  made  when  the 
aorta  was  tied  below  the  arch  and  arterial  blood  was  al- 
lowed to  circulate  in  the  head  and  anterior  extremities. 
I  believe  these  to  be  the  first  experiments  demonstrating 
positively  the  effects  of  depriving  the  respiratory  centre 
of  oxygen.  The  views  resulting  from  these  observations 
are  now  universally  accepted. 

Eighteen  hundred  and  sixty-two  is  the  date  of  the  pub- 
lication of  what  appears  in  these  volumes  as  Article  IX., 
on  a  "  New  Excretory  Function  of  the  Liver."  This  arti- 
cle was  published  in  French  in  1868.  In  1869  it  received 
an  "honorable  mention"  with  a  "recompense"  of  1,500 
francs  from  the  Institute  of  France  (Academic  des  Sci- 
ences), Concours  Monthyon  (medecine  et  chirurgie),  be- 
ing second  to  the  essay  by  Villemin,  on  the  specific  char- 
acter and  inoculabihty  of  tuberculosis,  the  most  important 


i 


PREFACE  ix 

work  in  medicine  since  the  discovery  of  vaccination,  which 
received  the  Monthyon  prize  for  that  year.  In  1876  I 
gave  an  abstract  of  my  work  in  an  address  before  the 
International  Medical  Congress  held  in  Philadelphia.  An- 
other abstract,  with  a  review  of  the  literature  since  1862, 
appeared  in  the  "  New  York  Medical  Journal,"  in  1877. 

I  mention  all  of  these  publications  in  this  place,  for 
the  reason  that  in  1896  an  article  appeared  in  Hoppe- 
Seyler's  "  Zeitschrift,"  in  which  most  of  my  experiments 
and  physiological  deductions  were  published  as  original 
by  two  workers  in  Schroeder's  Pharmacological  Institute 
in  Heidelberg. 

In  my  article  of  1862  I  described  a  new  substance  ex- 
tracted from  normal  feces,  which  I  called  stercorin.  I 
showed  that  this  substance  was  excrementitious  and  that 
it  resulted  from  a  change  of  the  cholesterin  of  the  bile  in 
its  passage  through  the  small  intestine,  incident  to  the 
process  of  intestinal  digestion;  that  cholesterin  was  prob- 
ably a  catabolic  product  of  nerve-tissue;  that  in  certain 
extensive  structural  diseases  of  the  liver,  the  proportion 
of  cholesterin  in  the  blood  was  largely  increased,  consti- 
tuting a  condition  which  I  called  cholesteremia;  and  that 
this  might  account  for  theretofore  unexplained  grave 
nervous  symptoms. 

The  chemists  who  claimed  to  have  discovered  a  new 
substance  in  the  feces  called  it  "  koprosterin."  They  ob- 
tained it  by  practically  the  same  process  employed  by  me 
for  the  extraction  of  stercorin,  in  1862.  The  only  varia- 
tions which  saved  their  method  from  being  identical  with 
the  process  employed  by  me  were  the  use  of  Soxhlet's 
extraction-apparatus,  not  known  in  1862,  by  which  the 
ethereal  extracts  were  made  more  rapidly,  and  the  re- 
moval of  fats  by  saponification  with  sodium  alcoholate 
instead  of  potassium  hydrate. 

In  1897,  in  the  Address  on  Medicine  at  the  semicen- 
tennial anniversary  of  the  American  Medical  Association, 


X  PREFACE 

I  gave  an  account  of  new  experiments  in  which  I  extracted 
stercorin  by  my  original  process  and  by  this  process  as 
modified  in  1896.  I  also  compared  the  two  products  with 
a  specimen  of  stercorin  extracted  in  1862,  w'hich  I  had 
fortunately  preserved,  verifying  the  empiric  formula  for 
each.  I  found  the  three  products  to  be  identical  as  to 
formula,  reactions  and  form  of  crystals. 

Later  in  1897  I  sent  these  facts  to  Hoppe-Seyler's 
"  Zeitschrift,"  w'ith  a  reclamation  of  priority,  which  were 
published  in  German  in  August  of  the  same  year.  The 
discoverers  of  "  koprosterin  "  denied  my  claim  of  the  iden- 
tity of  their  product  with  stercorin,  basing  this  denial  on 
a  statement  made  by  me  in  1862,  that  stercorin  fused  at  36° 
C.  "  Koprosterin  "  fuses  at  95°-96°.  In  1862  I  regarded 
stercorin  as  probably  identical  with  a  substance  which  had 
been  extracted  in  minute  quantity  from  the  serum  of  the 
blood,  by  Boudet,  called  seroline;  and  I  quoted  Lehmann 
as  giving  36°  as  its  fusing  point.  I  do  not  remember, 
after  an  interval  of  forty  years,  that  I  attempted  to  take 
the  fusing  point  of  the  stercorin  which  I  obtained  from 
feces. 

In  this  brief  analysis  I  have  simply  recited  facts  which 
I  trust  some  may  take  the  trouble  to  verify  by  referring 
to  the  articles  themselves;  and  I  have  no  desire  to  add 
what  can  be  regarded  as  in  any  degree  polemic.  Assum- 
ing a  familiarity  on  the  part  of  the  chemists  referred  to 
with  the  literature — which  was  not  denied — I  venture  only 
to  suggest,  as  a  possible  reason  why  the  pathological  as 
well  as  the  physiological  ideas  as  to  the  relations  of  ster- 
corin were  not  appropriated,  that  W'Orkers  in  pure  chem- 
istry can  hardly  be  expected  to  appreciate  the  importance 
of  such  researches  in  their  applications  to  practical  medi- 
cine. 

At  the  time  the  article  "  On  the  Organic  Nitrogenous 
Principles  of  the  Body  with  a  New  Method  for  their  Esti- 


PREFACE  xi 

mation  in  the  Blood  "  was  published  (1863),  all  the  anal- 
yses of  the  blood  to  be  found  in  works  on  physiology 
gave  estimates  of  dried  albumin,  fibrin  and  corpuscles. 
The  "  new  method  "  described  in  this  article  refers  chiefly 
to  estimates  of  albumin  and  fibrin.  Physiological  chem- 
ists, among  whom  may  be  mentioned  Dumas,  Denis, 
Figuier,  Becquerel  and  Rodier,  Schmidt,  and  Zimmer- 
mann,  had  attempted  to  estimate  the  corpuscles  in  their 
moist,  or  natural  condition.  In  my  analyses  for  organic 
nitrogenous  matters  I  obtained  the  proportions  of  moist 
albumin  and  fibrin;  but  physiologists  now  recognize,  in- 
stead of  albumin  and  fibrin,  a  number  of  proteids  in  the 
blood-plasma  that  had  not  been  described  in  1863.  I  suc- 
ceeded, employing  a  method  adapted  from  Figuier,  in 
estimating,  with  fair  accuracy,  the  corpuscles  in  their  nor- 
mal condition.  ]\Iany  attempts  to  do  this  had  been  made, 
by  processes  very  complex  and  uncertain.  Nearly  all 
works  on  physiology  now  give  the  proportion  of  moist 
corpuscles,  which  closely  corresponds  with  my  estimates; 
and  the  method  which  I  employed  was  so  simple  and  easy 
of  application  that  it  could  be  made  use  of  in  hospital 
or  private  practice.  Of  late  years,  however,  apparatus 
for  blood-counting  has  superseded  chemical  analysis  in 
clinical  work. 

The  remarkable  discovery  by  Bernard,  published  in 
1848,  of  what  he  called  the  sugar-producing  function  of 
the  liver  was  received  with  much  enthusiasm;  and  his  re- 
markable experiments  were  extensively  repeated  and  fre- 
quently used  as  demonstrations  in  the  teaching  of  physiol- 
ogy. A  few  years  later,  Pavy  claimed  to  have  demon- 
strated that  neither  the  liver  nor  the  blood  of  the  veins 
between  the  liver  and  the  heart  contains  sugar  during 
life;  and  that  the  sugar  found  by  Bernard  in  the  liver  and 
in  the  blood  of  the  hepatic  veins  was  the  result  of  post- 
mortem changfe  of  an  amvloid  substance.    This  latter  view 


xii  PREFACE 

found  main-  adherents,  parlicidaily  in  JuiL;land  and  Ger- 
many; so  that  in  \H(h)  tlie  (|iiestion  was  unsettled. 

In  1869  1  puhHshed  an  aecount  of  experiments  "  un- 
dertaken for  the  purpose  of  reconeihng-  some  of  the  dis- 
cordant observations  on  the  glycogenic  function  of  the 
liver."  These  experiments,  so  far  as  i  know,  were  the 
first  made  with  this  object.  In  1857  the  description  by 
Bernard  of  a  substance  in  the  liver,  called  glycogen,  which 
is  gradually  changed  into  sugar  by  a  ferment  and  is  car- 
ried away  as  sugar  by  the  liepatic  veins,  seemed  to  com- 
plete the  discovery  of  the  glycogenic  function.  In  my 
experiments  I  attempted  the  analysis  of  the  substance  of 
the  liver  in  a  condition  as  nearly  as  possible  approaching 
that  of  the  organ  actually  in  the  living  body.  I  opened 
the  abdomen  rapidly  and  cnt  a  portion  of  the  liver,  pre- 
viously rinsed  in  w^arm  w'ater,  into  boiling  water,  the  oper- 
ation lasting  but  ten  seconds.  I  found  no  sugar  in  the 
liver,  but  the  blood  of  the  hepatic  veins,  taken  from  the 
same  dog,  contained  sugar.  From  these  experiments  I 
concluded  that  during  life  the  liver  contains  no  sugar,  thus 
verifying  the  results  obtained  by  Pavy;  but  that  sugar 
resulting  from  a  transformation  of  glycogen,  as  fast  as  it 
is  formed,  is  w'ashed  out  by  the  blood-current  and  appears 
in  the  blood  of  the  hepatic  veins,  thus  confirming  the  re- 
sults obtained  by  Bernard.  My  experiments  seemed  to 
harmonize  the  apparently  discordant  observations  of  these 
tW'O  physiologists.  Since  that  time  it  has  been  the  gen- 
erally received  opinion  that  the  liver  stores  up  the  prod- 
ucts of  digestion  of  the  carbohydrates  in  the  form  of  gly- 
cogen, and,  in  the  carnivora  at  least,  produces  glycogen, 
probably  from  the  proteids;  and  that  glycogen  is  gradu- 
ally changed  into  sugar  wdiich  is  carried  away  in  the 
blood  of  the  hepatic  veins,  where  it  always  exists  during 
life.  In  the  experiments  recorded  in  this  article  portions 
of  the  liver  were  taken  from  living  animals  and  analyzed 
for  sugar  much  more  rapidly  than  in  any  previous  ob- 


PREFACE  xiii 

servations  with  which  I  am  acquainted.  These  experi- 
ments were  repeated  and  somewhat  extended  by  Lusk 
in  1870. 

The  ideas  in  regard  to  the  storing  up  of  the  carbo- 
hydrates of  food  in  the  hver  in  the  form  of  glycogen  and 
their  gradual  discharge  into  the  blood  in  the  form  of  sugar, 
which  these  and  other  observations  led  me  to  entertain, 
prompted  me  to  make  studies  of  the  relations  of  diet  to 
diabetes  mellitus,  the  results  of  which  appear  in  Articles 
XV.,  XVI.  and  XVII.,  published  in  1884  and  1887. 

In  1870  my  interest  in  physical  training  and  athletics 
led  me  to  witness  the  close  of  an  effort  by  a  professional 
pedestrian  to  walk  a  hundred  miles  in  twenty-two  con- 
secutive hours.  By  a  mere  chance  I  was  able  to  procure 
all  the  urine  said  to  have  been  passed  during  that  period. 
The  attempted  feat  of  endurance  was  accomplished;  and 
my  examination  of  the  urine  seemed  to  show  that  the  un- 
usual muscular  effort  largely  increased  the  elimination  of 
nitrogen  by  the  kidneys.  This  result  encouraged  me  to 
make  an  attempt  to  settle  the  disputed  question  of  the 
influence  of  muscular  work  on  the  elimination  of  nitrogen, 
by  a  carefully  prepared  and  much  more  elaborate  series 
of  investigations  on  the  same  person  in  an  attempt  to 
walk  four  hundred  miles  in  five  consecutive  days.  The 
details  of  these  observations,  made  in  the  fall  of  1870,  are 
embodied  in  Articles  XVIII.,  XIX.  and  XX.  The  results 
were  definite  and,  as  it  seemed  to  me,  conclusive.  I  com- 
pared the  outgo  with  the  income  of  nitrogen  for  three 
periods  of  five  days  each,  including  the  five  days  of  the 
walk. 

The  most  important  of  the  conclusions  related  to  the 
elimination  of  nitrogen  and  its  proportion  to  the  nitrogen 
of  the  food.  For  the  five  days  of  the  walk,  I  found  154 
parts  of  nitrogen  discharged  for  every  100  parts  of  nitro- 
gen of  food,  against  93  parts,  for  the  five  days  before  the 


xiv  PREFACE 

Avalk,  and  85  parts,  for  the  five  days  after  the  walk.  The 
investigations  which  formed  the  basis  of  these  articles  in- 
volved much  labor,  and  they  are  by  far  the  most  extensive 
ever  made  on  the  questions  considered.  However,  in  1876 
a  similar  series  of  observations  was  made  by  Dr.  Pavy,  of 
London,  upon  the  same  person,  in  a  walk  of  six  consecu- 
tive days.  The  general  results  of  these  experiments  con- 
firmed my  ow^n,  obtained  in  1870;  although  my  conclu- 
sions were  not  accepted,  on  theoretical  grounds. 

A  careful  study  of  the  observations  by  Dr.  Pavy  and 
others  led  me  to  publish,  in  1877,  the  essay  entitled 
"  Source  of  ^Muscular  Power,"  in  which  I  embodied  my 
own  investigations,  made  in  1870,  the  results  of  Dr.  Pavy's 
investigations,  made  in  1876,  with  a  discussion  of  experi- 
ments by  other  physiologists,  made  on  a  smaller  scale. 
Since  this  publication  it  has  appeared  that  certain  quoted 
estimates — at  the  best  of  doubtful  accuracy — used  in  my 
calculations,  probably  were  incorrect;  but  the  possible  er- 
rors involved  do  not  materially  afTect  the  general  conclu- 
sions.    Quoting  from  this  essay: 

"  I  feel  that  I  am  justified  in  claiming  priority  in  the 
method  of  investigating  the  influence  of  exercise  upon  the 
excretion  of  nitrogen  by  comparing  the  nitrogen  elim- 
inated with  the  nitrogen  of  food." 

As  my  experimental  data  seemed  opposed  to  the  views 
of  Pick  and  WisHcenus,  w^iich  were  then  quite  generally 
accepted,  the  observations  and  conclusions  of  Oppenheim, 
made  in  1880,  are  of  interest.  Oppenheim  concludes  that 
muscular  work,  when  not  carried  to  the  extent  of  pro- 
ducing shortness  of  breath  or  when  moderate  and  extend- 
ing over  a  considerable  length  of  time,  does  not  increase 
the  elimination  of  nitrogen;  but  that  even  less  work,  when 
violent  and  attended  with  shortness  of  breath,  increases 
the  discharge  of  nitrogen.  In  other  words,  when  the  in- 
creased elimination  of  carbon  dioxide,  due  to  muscular 
work,  has  reached  its  limit,  the  additional  work  is  repre- 


PREFACE  XV 

sented  by  an  increased  elimination  of  nitrogen.  An  ac- 
ceptance of  this  proposition  would  go  far  to  harmonize 
the  results  obtained  by  different  experimenters. 

Without  further  discussion  I  may  say  that  recent  ad- 
vances in  knowledge  of  the  phenomena  of  nutrition  and 
catabolism  do  not  seem  to  have  impaired,  in  any  impor- 
tant degree,  the  value  of  my  experiments  and  conclusions 
made  thirty-two  years  ago. 

The  researches  which  formed  the  basis  of  the  articles 
upon  the  influence  of  muscular  work  on  the  elimination 
of  nitrogen  and  the  essay  on  the  source  of  muscular  power 
naturally  led  to  a  study  of  animal  heat  and  the  applications 
of  the  theories  of  calorification  to  fever  and  its  rational 
treatment.  In  discussing  the  source  of  muscular  power 
I  made  use  of  the  estimate  by  Senator,  of  the  probable 
production  of  four  heat-units  per  hour  per  pound  of  body- 
weight;  and  the  same  estimate  was  adopted  in  the  article, 
"  Experiments  and  Reflections  on  Animal  Heat,"  pub- 
lished in  1879.  With  this  estimate — which  I  regarded  as 
not  entirely  reHable — it  seemed  impossible  to  account  for 
the  heat  thus  assumed  to  be  actually  produced  and  either 
used  or  lost  by  radiation,  by  the  heat-value  of  food.  Even 
with  the  estimate,  made  by  the  indirect  method,  of  two 
and  a  half  heat-units  per  pound  per  hour,  it  was  difficult 
to  account  for  the  heat  produced,  by  the  heat-value  of 
the  processes  usually  regarded  as  involved  m  calorifica- 
tion. 

Assuming  that  the  total  heat  produced  in  the  body, 
deducting  the  loss  by  heat-dissipation,  is  used  to  maintain 
the  animal  temperature  and  to  accomplish  work,  the  ele- 
ments in  the  problem  of  its  expenditure  are  discouragingly 
uncertain  as  regards  estimates  of  the  quantities  converted 
into  force  to  maintain  circulation  and  respiration  and  to 
accomplish  general  muscular  work.  The  most  important 
element  in  this  problem,  however,  is  the  estimation  of  the 
actual  quantity  of  heat  produced  per  pound  of  body-weight 


xvi  PREFACE 

per  hour;  and  a  fairly  accurate  estimate  of  this  would  ren- 
der calculations  of  the  proportion  lost,  the  proportion  used 
as  force  and  to  maintain  the  body  temperature  compara- 
tively unimportant  in  ascertaining  the  sources  of  heat- 
production  and  muscular  power;  assuming,  as  we  must, 
the  validity  of  the  law  of  the  correlation  and  conservation 
of  forces.  But  with  the  lowest  estimates  of  heat  expended 
as  force,  it  is  difficult,  if  not  impossible  to  account  for  it 
by  the  heat-value  of  food  or  tissue  consumed,  represented 
by  the  excreta,  assuming  anything  near  accuracy  in  these 
measurements.  To  solve  the  problem,  even  approxi- 
mately, it  is  necessary  to  find  sources  of  heat  which  will 
much  more  than  account  for  the  work,  reduced  back 
from  force-units  to  heat-units,  the  maintenance  of  body- 
heat  and  the  loss  by  heat-dissipation. 

The  difficulties  that  I  have  indicated  in  a  measure  ac- 
count for  the  indeffiiite,  not  to  say  obscure  manner  in 
which  the  subject  of  animal  heat  and  force  is  treated  in 
nearly  all  modern  systematic  treatises  on  physiology.  In 
general  terms,  it  may  be  said  that  the  indirect  method  of 
estimating  heat-production  is  to  calculate  the  heat-value 
of  oxygen  taken  in  and  correct  this  by  comparing  it  with 
the  heat-value  represented  by  oxidized  matters  discharged. 
This  has  been  found  to  correspond  fairly  well  with  the  cal- 
culated heat-value  of  food.  Such  a  calculation,  however, 
almost  begs  the  question;  it  simply  indicates  what  should 
be  the  heat-production  and  assumes  that  the  heat-pro- 
duction is  what  the  calculations  show  that  it  should  be. 
The  strictly  logical  process  is  the  direct  method,  using 
the  calorimeter,  and  measuring,  if  possible,  the  heat  ac- 
tually produced.  By  the  indirect  method,  the  calculated 
heat-production  about  equals  the  calculated  heat-value  of 
food,  with  the  body  in  a  condition  of  physiological  equilib- 
rium; but  the  food  accounts  for  only  about  62^  per  cent, 
of  the  heat  actually  produced,  calculated  by  the  direct 
method.     With  the  very  large  elements  of  uncertainty  in 


PREFACE  xvii 

the  reduction  of  the  force  used  in  circulation  and  respira- 
tion and  in  general  muscular  work  to  heat-units,  the  ques- 
tion of  heat  and  force-production  in  the  body  seems  as 
far  from  a  satisfactory  solution  to-day  as  it  was  before 
1879. 

Although  Lavoisier  and  Laplace,  in  1780  and  1785, 
had  attributed  heat-production  to  oxidation  of  carbon  and 
hydrogen,  it  had  never  been  demonstrated,  before  my  ex- 
periments published  in  1879,  that  oxygen  actually  unites 
in  the  body  with  hydrogen  to  form  water.  The  heat-value 
of  such  oxidation  is  very  great;  and  this,  added  to  the 
heat  represented  by  the  carbon  dioxide,  urea,  etc.,  eHm- 
inated,  would  much  more  than  account  for  the  heat  ac- 
tually produced  and  used  either  as  heat  or  as  force,  making 
the  calculations  of  heat  produced,  either  by  the  direct  or 
by  the  indirect  method.  The  increase  in  the  production 
of  water  due  to  increased  muscular  work  also  would  ac- 
count for  the  necessary  increase  in  the  production  of  heat 
to  supply  the  force. 

I  think  I  was  the  first  to  demonstrate  positively  by 
experiments,  some  of  which  were  made  on  my  own  per- 
son, that  under  conditions,  at  least,  when  oxidation  repre- 
sented by  carbon  dioxide  and  nitrogenous  excretions  is 
not  sufficient  to  supply  the  heat  required,  water  is  pro- 
duced in  the  body,  as  is  shown  by  a  considerable  excess 
of  water  discharged  over  and  above  the  water  taken  in, 
without  loss  of  water  by  the  liquids  and  tissues  of  the  or- 
ganism. I  could  thus  account,  also,  for  the  oxygen  of  the 
respired  air  lost  and  not  represented  in  carbon  dioxide  and 
other  excreta. 

At  the  ninth  session  of  the  International  Medical  Con- 
gress, held  in  Washington  in  1887,  addresses  were  made 
in  general  session  by  representatives  of  Great  Britain, 
France,  Austria,  Germany,  Italy  and  the  United  States. 
I  was  honored  with  the  appointment  to  deliver  the  ad- 
dress in  behalf  of  the  United  States;  and  I  chose  the  sub- 


xviii  PREFACE 

ject  of  "  Fever."  In  this  address  I  endeavored  to  apply 
my  studies  in  animal  heat  to  the  mechanism  and  rational 
treatment  of  fever,  especially  in  the  way  of  supplying  ma- 
terial to  feed  the  fever  and  save  the  tissues  until  the  dis- 
ease should  have  run  its  self-limited  course,  restricting, 
also,  the  destruction  and  degenerations  of  tissue  by  re- 
ducing temperature.  I  took  the  ground  that  in  certain 
cases  it  became  necessary  to  "  feed  the  fever  "  with  al- 
cohol. 

There  has  been,  is  at  the  present  time  and  probably 
will  be  far  into  the  future,  violent  and  acrimonious  dis- 
cussion as  to  the  fate  of  alcohol  taken  into  the  body.  The 
main  question  now  agitated  is  whether  or  not  alcohol, 
taken  in  quantity  not  sufficient  to  produce  intoxication, 
is  oxidized  and  serves  as  food  or,  if  not  directly  as  food, 
as  an  agent  restricting  the  waste  of  tissue.  A  controversy 
between  the  laity,  opposed  on  moral  grounds  to  the  use  of 
alcohol,  and  scientific  observers  not  practically  familiar 
with  disease  and  its  treatment  but  relying  on  studies  of  the 
changes  which  alcohol  undergoes  in  the  healthy  organism, 
is  not  likely  to  promote  a  scientific  solution  of  the  question 
involved.  While  it  may  be  that  in  a  healthy  person,  ade- 
quately nourished,  alcohol  is  not  useful,  even  if  not  ac- 
tually harmful,  and  that  it  can  not  contribute,  except  mo- 
mentarily, to  mental  or  physical  power  and  endurance, 
in  its  judicious  and  careful  therapeutic  administration,  in 
many  diseases,  it  is  often  of  great  value.  I  therefore  ad- 
here to  the  views  embodied  in  the  two  articles  on  fever 
and  in  the  article  "  On  Some  of  the  Therapeutic  Uses  of 
Alcohol,"  published  in  1887. 

It  is  calculated  that  10  grains  of  absolute  alcohol, 
when  oxidized,  will  produce  23  heat-units;  and  one 
ounce,  weighing  about  384  grains,  is  equal  to  about 
883  heat-units.  In  fever  alcohol  administered  in  certain 
quantity  is  not  eliminated  as  alcohol:  it  does  not  intoxi- 
cate and,  as  it  seems,  it  must  be  oxidized.     Thus  admin- 


PREFACE 


XIX 


istered  it  does  not  increase  pyrexia;  and  if  oxidized,  it 
must  save  tissue  and  moderate  degenerations.  If  these 
statements  are  true,  alcohol  can  not  properly  be  eliminated 
from  therapeutics  any  more  than  morphin  or  strychnin. 

While  I  have  thought  it  well,  for  the  benefit  of  those 
who  may  be  led  to  read  some  of  the  articles  here  repub- 
lished, to  give,  in  a  brief  analysis,  a  rather  more  extended 
account  of  what  is  contained  in  these  volumes  than  is  to 
be  found  in  the  Table  of  Contents,  I  have  not  intended 
to  refer  to  individual  articles  unless  they  presented  some 
claim  to  original  investigation  or  to  unusual  methods  of 
treatment  of  the  subjects  considered.  In  the  three  articles 
on  examination  of  urine  I  insisted  on  the  importance  of 
examinations  in  all  cases  of  application  for  life  insurance, 
which  was  rarely  done  at  the  time  I  became  a  medical 
examiner  for  a  large  company,  in  1871.  An  experience 
of  fifteen  years  in  such  work  confirmed  me  in  this  judg- 
ment. I  endeavored,  also,  to  popularize  in  the  profession 
urinary  examinations  by  the  general  practitioner,  by  pre- 
senting rapid  and  easy  methods  sufficiently  accurate  for 
ordinary  clinical  purposes. 

In  1888  I  reported  a  case,  in  Article  XXXII.,  of  sci- 
atica treated,  with  very  prompt  relief,  with  doses  of  anti- 
febrin  much  larger  than  ever  used  before. 

I  may  also  refer  briefly  to  a  "  Tonic  Formula  "  (Article 
XXXIII. ),  which  has  been  largely  used  since  the  publica- 
tion of  this  article  in  1889.  In  calculating  this  formula 
I  endeavored  to  make  a  preparation  containing  the  inor- 
ganic constituents  of  the  blood  in  about  the  normal  pro- 
portions, with  an  excess  of  iron  and  of  sodium  chloride, 
to  be  used  as  a  remedy  in  certain  cases  in  which  it  seemed 
to  me  that  patients  were  suffering  from  deficiency  in  saline 
matters  as  well  as  corpuscles.     My  own  experience  with 


XX  PREFACE 

the  "  Saline  and  Chalybeate  Tonic  "  has  been  quite  satis- 
factory; and  I  have  lately  seen  an  imitation  of  the  formula 
recommended  for  the  purpose  I  have  indicated. 

The  so-called  "  Frenchy  "  murder  trial,  in  1891,  ex- 
cited at  the  time  great  professional  and  popular  interest, 
on  account  of  the  peculiar  atrocity  of  the  crime,  the  sav- 
age character  and  history  of  the  accused  and  the  very  un- 
usual nature  of  the  expert  testimony.  The  evidence  in 
this  case  was  entirely  circumstantial;  and  there  is  now 
much  difference  of  opinion  in  regard  to  the  justice  of  the 
verdict.  This  case  was  again  brought  to  public  notice  by 
the  release  of  the  prisoner  after  eleven  years  of  confine- 
ment under  a  life  sentence  for  murder  in  the  second  de- 
gree, part  of  the  time  in  the  Asylum  for  Insane  Criminals. 
The  very  last  article  of  this  collection  gives  a  brief  retro- 
spect of  the  case,  written  on  the  occasion  of  the  action 
of  the  Governor  of  the  State  of  New  York. 

The  verdict  of  the  jury  rested  practically  on  testimony 
as  to  recognizable  differences  between  the  contents  of  the 
small  and  of  the  large  intestine,  small  portions  of  which 
were  found  about  the  person  of  the  victim  and  the  person 
of  the  accused,  including  matters  taken  from  beneath  the 
finger  nails.  "  The  evidence  which  convicted  the  prisoner 
was  that  the  various  specimens  examined  by  the  experts 
for  the  people  presented  blood  mixed  with  matters  which 
must  have  come  from  the  small  intestine,  and  which  by 
no  reasonable  theory,  could  be  on  the  prisoner's  clothing 
and  person  unless  they  came  from  the  body  of  the  mur- 
dered worrian.  It  is  this  point  in  the  case  which,  so  far 
as  I  know,  is  without  precedent  and  is  of  peculiar  medico- 
legal interest." 

It  is  to  be  regretted  that  a  full  report  of  this  case  has 
never  been  published  and  that  my  own  testimony  is  all 
that  has  appeared.  So  far  as  expert  work  is  concerned, 
the  case  is  unique. 


PREFACE  xxi 

Late  in  1892  I  began  to  use  bismuth  subgallate  in  so- 
called  functional  dyspepsia  attended  with  gastric  and  in- 
testinal flatulence.  I  was  led  to  the  use  of  this  remedy  by 
seeing  it  recommended  for  the  diarrhea  of  children,  acting 
as  a  disinfectant.  I  think  I  was  the  first  to  administer  it 
in  ordinary  digestive  disturbances.  It  is  now  very  ex- 
tensively prescribed,  and  the  general  experience  in  regard 
to  its  value  as  an  antifermentative  is  in  accord  with  my 
own. 

The  case  of  "  Filaria  "  with  chyluria  (Article  XXXVI.), 
reported  in  1895,  is  the  first  on  record  in  which  methylene 
blue  was  employed  with  the  view  of  destroying  this  re- 
markable nocturnal  parasite.  I  advised  this  remedy  in  the 
•case  reported,  reasoning  from  my  experience  in  its  action 
on  the  Plasmodium  malarise.  It  w^as  suggested  in  this 
article  that  there  was  a  "  possibility  of  benefit  from  methy- 
lene blue  in  the  treatment  of  other  diseases  due  to  the 
filaria,  such  as  chylous  collections  in  the  peritoneal  cavity 
and  in  the  cavity  of  the  tunica  vaginaHs  testis,  hematuria 
and  elephantiasis." 

In  1867,  at  the  request  of  the  then  Commissioners  of 
Public  Charities  and  Correction  of  the  City  of  New  York, 
I  made  an  examination  of  the  food  supplies  and  methods 
of  cooking  and  serving  in  Bellevue  Hospital  and  in  the 
other  hospitals,  prisons,  etc.,  under  their  charge.  This 
resulted  in  the  recommendation  of  the  dietaries  embodied 
in  Article  XXXVII.  It  is  almost  unnecessary  to  say 
that  for  many  years,  the  sick  poor,  the  pauper  insane, 
prisoners  and  others,  including  infants  and  children,  under 
the  care  of  the  City  and  State  have  been  subject  to  the 
vicissitudes  of  politics.  They  sutifer,  on  the  one  hand,  from 
the  ignorance  or  indifference  of  administration,  and  on 
the  other,  from  w^ell-meant  efforts  of  dietetists  to  reduce 
nutritive  supply  to  the  calculated  requirements  of  nitrogen 


xxii  PREFACE 

and  carbon.  It  is  fair  to  say  that  the  dietaries  suggested 
were  for  a  time  carried  out  as  fully  as  possible  under  the 
then  existing  methods  of  purchase  of  supplies  and  of  ap- 
pointment of  subordinate  officers;  but  the  many,  and  some- 
times revolutionary  changes  in  administration,  that  have 
occurred  since  1867,  have  led  to  such  modifications  in 
these  dietaries  that  their  original  character  has  long  since 
disappeared.  I  take  this  opportunity,  however,  again  to 
express  my  confidence  in  dietaries  constructed  on  physi- 
ological rather  than  on  purely  chemical  principles  applied 
to  metabolism;  a  belief  which  I  think  is  shared  by  physi- 
cians familiar  with  disorders  in  general  nutrition  so  often 
seen  in  private  practice  as  well  as  in  hospitals,  asylums 
and  prisons. 

I  also  prepared  dietaries  for  the  State  Hospitals  for  the 
Insane,  in  1893,  the  population  of  which  considerably  ex- 
ceeded twenty  thousand.  These  dietaries  were  placed  on 
trial  for  one  year.  They  were  then  revised  in  accordance 
with  suggestions  and  recommendations  made  by  the  Su- 
perintendents of  the  different  hospitals.  The  revised  re- 
port is  republished  as  Article  XXXVIII. 

In  1898  there  was  a  change  in  the  personnel  of  the 
State  Commission  in  Lunacy;  and  the  dietaries  in  opera- 
tion since  1894  were  superseded  on  the  ground  of  economy. 
I  can  not  question  the  wisdom  of  this  change,  for  lack  of 
information  in  regard  to  the  experience  with  the  new 
schedules;  although  very  elaborate  tables  showing  the  cal- 
culated nutritive  requirements  were  published  in  1899  and 
1900,  in  which  it  appeared  that  these  requirements  could 
be  adequately  met  by  the  calculated  nutritive  values  of 
supplies  less  than  those  in  use.  Still  another  change  oc- 
curred, in  December,  1900,  when  the  President  of  the 
Commission,  appointed  in  1898,  was  removed  by  the  Gov- 
ernor. The  dietaries  were  again  more  or  less  modified 
under  the  new  administration;  but  I  have  little  or  no  in- 
formation as  to  the  nature  of  these  changes. 


PREFACE  xxiii 

In  1895,  at  the  request  of  the  Comptroller  of  the  State 
of  New  York,  I  prepared  schedules  of  diet  for  the  various 
State  charitable  and  reformatory  institutions  reporting  to 
the  Comptroller's  Office.  These  were  made  on  the  same 
general  lines  as  those  of  the  dietaries  for  the  State  hos- 
pitals, but  with  certain  modifications  that  are  indicated 
in  Article  XXXIX.  These  dietaries,  however,  were  never 
put  into  operation,  and  they  are  now  published  for  the 
first  time. 

I  was  appointed  by  the  Governor  of  the  State  of  New 
York,  in  1894,  the  medical  member  of  a  commission  of 
three  to  investigate  the  administration  of  the  New  York 
State  Reformatory  at  Elmira,  in  view-  of  certain  charges 
brought  against  the  General  Superintendent.  I  was  the 
joint  author,  with  the  Hon.  Israel  T.  Deyo,  of  the  major- 
ity report  of  this  commission,  w'hich  was  adopted  by  the 
Governor.  This  report  is  not  republished  in  these  volumes 
for  the  reason  that  I  was  not  its  sole  author;  but  I  am 
glad  to  have  the  opportunity  of  putting  myself  again  on 
record  as  approving  the  reformatory  system,  especially  as 
it  was  carried  out  at  Elmira.  Article  LIX.,  on  the  "  Sci- 
entific Treatment  of  Crime  and  Criminals,"  and  Article 
LX.,  "  The  Pain  of  Death,"  embody  most  of  the  features 
of  this  report  that  are  of  interest  to  the  medical  profession 
and  to  criminologists. 

I  am  also  more  than  ready  to  go  on  record  as  opposed 
to  capital  punishment.  My  view's  on  this  question — one 
of  great  importance  to  our  social  system — are  contained 
in  the  address  on  "  The  Pain  of  Death,"  before  the  "  Quill 
Club,"  made  in  1897. 

What  I  have  just  written  completes  the  analysis  of  the 
strictly  scientific  essays  and  articles.  In  addition  to  these 
are  twenty-one  magazine  articles,  which  have  appeared 
in  various  periodicals  between  1866  and  1901,  including 


xxiv  PREFACE 

two  ("  Gymnastics  "  and  "  Pugilism  ")  published  in  the 
"American  Cyclopaedia,"  in  1874  and  1875.  In  these  arti- 
cles I  attempted  the  difficult  task  of  popularizing  certain 
scientific  subjects.  Many  of  the  titles  are  not  my  own 
but  were  suggested  by  editors.  I  do  not  feel  competent 
to  decide  whether  or  not  my  efforts  to  clothe  scientific 
questions  in  popular  language  and  style  have  been  suc- 
cessful. Articles  LIV.,  LV.  and  LVL,  however,  are  more 
serious  than  some  of  those  classed  as  "  Miscellaneous." 
They  were  published  in  "  The  Forum  "  in  1888,  1889  and 
1891  and  are  devoted  mainly  to  bacteriology  and  its  bear- 
ing on  the  recent  remarkable  progress  in  medicine  and 
surgery.  It  is  gratifying  to  see  that  many  of  the  predic- 
tions which  I  ventured  to  make  at  the  time  these  articles 
were  written,  when  the  bacterial  theories  of  disease  were 
in  their  infancy,  have  since  been  realized.  Studies  in  bac- 
teriology, dating  from  the  discovery  of  the  tubercle  ba- 
cillus by  Koch,  in  1882,  excited  much  popular  as  well  as 
scientific  interest;  and  "  The  Forum  "  was  one  of  the  first 
of  the  magazines  devoted  to  general  literature  to  publish 
articles  on  this  subject. 

The  rather  formidable  list  following  the  name  on  the 
title  page  would,  perhaps,  be  out  of  place,  except  as  repre- 
senting a  personal  professional  history  in  volumes  which 
include  all  my  literary  work  up  to  the  present  date. 

New  York,  November,  igo2. 


CONTENTS   OF   VOLUME   FIRST 


ESSAYS    AND    ARTICLES    ON    PHYSIOLOGY   AND 
MEDICINE 

I 

PAGE 

AN    ANALYSIS    OF    ONE    HUNDRED    AND    SIX   CASES    OF 

PARONYCHIA i 

Published  in  the  "Buffalo  Medical  Journal"  for  October,  1S55. 

II 

PHENOMENA  OF  THE  CAPILLARY  CIRCULATION— AN 
INAUGURAL  DISSERTATION  LAID  BEFORE  THE  FAC- 
ULTY   OF    THE    JEFFERSON     MEDICAL     COLLEGE     IN 

FEBRUARY,   1857 11 

Published  in  the  "American  Journal  of  the  Medical  Sciences"  for 
July,  1857. 

Ill 

EXPERIMENTS    ON    THE    RECURRENT    SENSIBILITY    OF 

THE   ANTERIOR    ROOTS    OF   THE    SPINAL    NERVES        .       29 
Published  in  the  "New  Orleans  Medical  Times,"  in  1861. 

IV 

HISTORICAL  CONSIDERATIONS  CONCERNING  THE  PROP- 
ERTIES  OF    THE    ROOTS    OF    THE    SPINAL    NERVES      .       35 
Published  in  the  "  Quarterly  Journal  of  Psychological  Medicine  "  for 
October,  i863. 


EXPERIMENTAL    RESEARCHES    ON    POINTS   CONNECTED 
WITH     THE     ACTION     OF     THE     HEART     AND     WITH 

RESPIRATION 61 

Published  in  the  "  American  Journal  of  the  Medical  Sciences"  for 
October,  1861. 

XXV 


PAGE 


xxvi  CONTENTS    OF    VOLUME    FIRST 

VI 

MECHANISM    OF     REFLEX     NERVOUS    ACTION    IN     NOR- 
MAL   RESPIRATION— AN     ADDRESS    DELIVERED    FEB- 
RUARY   i6,    1874,    BEFORE    THE    NEW    YORK     SOCIETY 
OF    NEUROLOGY   AND    ELECTROLOGY         .         .         .         .112 
Published  in  the  "  Chicago  Journal  of  Nervous  and  Mental 
Diseases  "  for  April,  1874. 

VII 

EXPERIMENTS    ON    THE     EFFECTS    UPON    RESPIRATION 
OF     CUTTING     OFF     THE     SUPPLY    OF    BLOOD     FROM 
THE    BRAIN    AND    MEDULLA   OBLONGATA         .         .         .124 
Published  in  the  "  New  York  Medical  Journal"  for  November,  1877. 

VIII 

IS    THE    ACTION     OF    THE     MEDULLA     OBLONGATA     IN 

NORMAL    RESPIRATION    REFLEX? 136 

Published  in  the  "  American  Journal  of  the  Medical  Sciences  "  for 
July,  1880. 

IX 

EXPERIMENTAL  RESEARCHES  INTO  A  NEW  EXCRETORY 
FUNCTION  OF  THE  LIVER;  CONSISTING  IN  THE  RE- 
MOVAL OF  CHOLESTERIN  FROM  THE  BLOOD,  AND 
ITS  DISCHARGE  FROM  THE  BODY  IN  THE  FORM  OF 
STERCORIN.  (THE  SEROLINE  OF  BOUDET.)  .  .  .163 
Published  in  the  "  American  Journal  of  the  Medical  Sciences"  for 
October,  1S62. 

X 

THE    EXCRETORY    FUNCTION    OF    THE    LIVER      .         .         .239 

Published  in  the  "  Transactions  of  the  International  Medical 

Congress,"  held  in  Philadelphia  in  September,  1876. 

XI 

STERCORIN    AND    CHOLESTEREMIA 258 

Published  in  the  "  New  York  Medical  Journal  "  for  June  5,  1897. 

XII 
UEBER    STERCORIN 272 

Published  in  Hoppe-Seyler's  "  Zeitschrift  fiir  physiologische 
Chemie,"  August  28,  1897. 


CONTENTS   OF   VOLUME   FIRST  xxvii 

XIII 

PAGE 

ON  THE  ORGANIC  NITROGENOUS  PRINCIPLES  OF  THE 
BODY  WITH  A  NEW  METHOD  FOR  THEIR  ESTIMA- 
TION   IN    THE    BLOOD 277 

Published  in  the  "  American  Journal  of  the  Medical  Sciences"  for 
October,  1863. 

XIV 

EXPERIMENTS  UNDERTAKEN  FOR  THE  PURPOSE  OF 
RECONCILING  SOME  OF  THE  DISCORDANT  OBSERVA- 
TIONS ON  THE  GLYCOGENIC  FUNCTION  OF  THE 
LIVER 315 

Published  in  the  "  New  York  Medical  Journal"  for  November, 
i86q. 


XV 

THE   TREATMENT   OF   DIABETES    MELLITUS        .         .         .323 

Published  in  the  "Journal  of  the  American  Medical  Association" 
for  July  12,  1884. 


XVI 

FOUR  SELECTED  TYPICAL  CASES  OF  DIABETES  MEL- 
LITUS   NOT   BEFORE    REPORTED 349 

Published  in  the  "  New  York  Medical  Journal  "  for  November  22, 

1884. 

XVII 

LITHIUM  CARBONATE  AND  SODIUM  ARSENATE  DIS- 
SOLVED IN  CARBONIC  ACID  WATER  IN  THE  TREAT- 
MENT  OF    DIABETES    MELLITUS 356 

Published  in  the  "  Medical  News"  for  July  9,  1887. 

XVIII 

THE  INFLUENCE  OF  EXCESSIVE  AND  PROLONGED  MUS- 
CULAR EXERCISE  ON  THE  ELIMINATION  OF  EF- 
FETE   MATTERS    BY   THE    KIDNEYS 366 

Published  in  the  "  New  York  Medical  Journal  "  for  October,  1870. 


PAGE 


xxvi  CONTENTS    OF   VOLUME   FIRST 

VI 

MECHANISM    OF    REFLEX     NERVOUS    ACTION     IN     NOR- 
MAL   RESPIRATION— AN     ADDRESS     DELIVERED    FEB- 
RUARY   i6,    1S74,    BEFORE    THE    NEW    YORK     SOCIETY 
OF    NEUROLOGY   AND    ELECTROLOGY         ....     112 
Published  in  the  "  Chicago  Journal  of  Nervous  and  Mental 
Diseases  "  for  April,  1874. 

VII 

EXPERIMENTS    ON    THE     EFFECTS    UPON    RESPIRATION 
OF     CUTTING     OFF     THE     SUPPLY    OF     BLOOD     FROM 
THE    BRAIN    AND    MEDULLA   OBLONGATA         .         .         .12+ 
Published  in  the  "  New  York  Medical  Journal"  for  November,  1877. 

VIII 

IS    THE    ACTION     OF    THE     MEDULLA     OBLONGATA     IN 

NORMAL    RESPIRATION    REFLEX? 136 

Published  in  the  "  American  Journal  of  the  Medical  Sciences  "  for 
July,  1880. 

IX 

EXPERIMENTAL  RESEARCHES  INTO  A  NEW  EXCRETORY 
FUNCTION  OF  THE  LIVER;  CONSISTING  IN  THE  RE- 
MOVAL OF  CHOLESTERIN  FROM  THE  BLOOD,  AND 
ITS  DISCHARGE  FROM  THE  BODY  IN  THE  FORM  OF 
STERCORIN.  (THE  SEROLINE  OF  BOUDET.)  .  .  .163 
Published  in  the  "  American  Journal  of  the  Medical  Sciences"  for 
October,  1862. 

X 

THE    EXCRETORY    FUNCTION    OF   THE    LIVER      .         .         .239 

Published  in  the  "  Transactions  of  the  International  Medical 

Congress,"  held  in  Philadelphia  in  September,  1876. 

XI 

STERCORIN    AND    CHOLESTEREMIA 258 

Published  in  the  "  New  York  Medical  Journal  "  for  June  5,  1897. 

XII 
UEBER    STERCORIN 272 

Published  in  Hoppe-Seyler's  "  Zeitschrift  fur  physiologische 
Chemie,"  August  28,  1897. 


CONTENTS   OF   VOLUME   FIRST 


XIII 


PAGE 


ON  THE  ORGANIC  NITROGENOUS  PRINCIPLES  OF  THE 
BODY  WITH  A  NEW  METHOD  FOR  THEIR  ESTIMA- 
TION   IN    THE    BLOOD 277 

Published  in  the  "  American  Journal  of  the  Medical  Sciences"  for 
October,  1S63. 

XIV 

EXPERIMENTS  UNDERTAKEN  FOR  THE  PURPOSE  OF 
RECONCILING  SOME  OF  THE  DISCORDANT  OBSERVA- 
TIONS ON  THE  GLYCOGENIC  FUNCTION  OF  THE 
LIVER 315 

Published  in  the  "  New  York  Medical  Journal "  for  November, 
1869. 

XV 

THE   TREATMENT   OF    DIABETES    MELLITUS         .         .         .323 

Published  in  the  "Journal  of  the  American  Medical  Association" 
for  July  12,  1884. 


XVI 

FOUR  SELECTED  TYPICAL  CASES  OF  DIABETES  MEL- 
LITUS   NOT    BEFORE    REPORTED 349 

Published  in  the  "New  York  Medical  Journal  "  for  November  22, 

18S4. 

XVII 

LITHIUM  CARBONATE  AND  SODIUM  ARSENATE  DIS- 
SOLVED IN  CARBONIC  ACID  WATER  IN  THE  TREAT- 
MENT  OF    DIABETES    MELLITUS 356 

Published  in  the  "  Medical  News"  for  July  9,  1887. 

XVIII 

THE  INFLUENCE  OF  EXCESSIVE  AND  PROLONGED  MUS- 
CULAR EXERCISE  ON  THE  ELIMINATION  OF  EF- 
FETE   MATTERS    BY   THE    KIDNEYS 366 

Published  in  the  "  New  York  Medical  Journal  "  for  October,  1870. 


xxviii  CONTENTS   OF   VOLUME    FIRST 

XIX 

PAGE 

ON    THE    EFFECTS   OF   SEVERE  AND    PROTRACTED    MUS- 
CULAR     EXERCISE;    WITH     SPECIAL    REFERENCE    TO 
ITS    INFLUENCE    ON    THE    EXCRETION    OF    NITROGEN     375 
Published  in  the  "  New  York  Medical  Journal"  for  June,  1871. 

XX 

SUPPLEMENTARY  REMARKS  ON  "THE  EFFECTS  OF  SE- 
VERE AND  PROTRACTED  MUSCULAR  EXERCISE; 
WITH    SPECIAL    REFERENCE   TO    ITS    INFLUENCE    ON 

THE    EXCRETION    OF    NITROGEN" 461 

Published  in  the  "  Journal  of  Anatomy  and  Physiology,"  Cambridge 
and  London,  for  October,  1876. 


I 

AN   ANALYSIS    OF    ONE    HUNDRED   AND    SIX 
CASES    OF    PARONYCHIA 

Published  in  the  "  Buffalo  Medical  Journal "  for  October,  1855. 
PARONYCHIA    BENIGNA 

The  private  records  of  Dr.  F.  H.  Hamilton  contain 
■eighty-one  cases  of  paronychia  benigna. 

In  all  these  cases  the  sex  has  been  noted,  and  the  pro- 
portion of  females  to  males  is  nearly  two  to  one,  there  being 
fifty-three  females  and  twenty-eight  males.  In  considering 
the  occupation  of  these  patients  and,  as  far  as  could  be  as- 
certained, the  causes  which  operated  to  produce  the  dis- 
ease, in  the  great  majority  of  cases  it  was  found  that  the 
•occupation  involved  manual  labor;  and  where  the  occupa- 
tion was  noted  as  the  cause  of  the  disease,  it  was  most  fre- 
quently an  occupation  in  which  females  are  generally  en- 
g'aged.  In  the  male  patients,  the  cause  w^as  generally  a 
bruise  or  slight  injury  to  one  of  the  fingers  and  not  the  oc- 
cupation. As  feminine  duties  frequently  cause  paronychia 
and  accidental  injuries  are  the  most  frequeftt  causes  in  the 
male  subject,  it  is  not  surprising  to  find  a  larger  proportion 
■of  cases  occurring  in  females. 

In  sixty-one  cases  the  hand  affected  with  the  parony- 
chia was  designated. 

Of  these  cases  forty-two  occurred  on  the  right  hand 
and  nineteen  on  the  left;  showing  that  the  right  hand, 
being  more  used  and  more  subject  to  accidental  injuries, 
is  much  more  liable  to  this  affection. 

In  seventy-five  cases  the  diseased  finger  was  designated. 
The  thumb  and  first  finger,  which  are  most  used,  were 
affected  in  the  greatest  proportion  of  cases  and  appeared 
to  be  about  equally  liable  to  the  disease.  The  thumb  was 
the  seat  of  the  affection  in  thirty-two  cases  and  the  first 
I  I 


2  ANALYSIS   OF   CASES   OF   PARONYCHIA 

finger  in  twenty-seven.  The  second  finger  was  next  in 
order,  being  affected  in  ten  cases.  There  were  but  two 
cases  affecting  the  third  finger;  one  affecting  the  fourth 
finger;  two  affecting  the  first,  second  and  third;  and  one 
affecting  the  second  and  third.  The  last  three  cases  were 
of  the  first  variety,  onychia  cutanea.  One  of  them  was 
caused  by  pricking  the  finger  in  sewing.  This  was  very 
trivial  and  got  well  spontaneously.  The  other  two  were 
caused  by  suppressed  menses  and  were  soon  cured  by 
nitrate  of  silver  and  poultices.  Thus,  not  only  the  hand, 
but  the  fingers  which  are  most  used  are  most  liable  to 
paronychia. 

In  sixty-three  cases  the  ages  of  the  patients  were 
noted. 

I  found  but  three  cases  under  fifteen  years  of  age.  One 
of  these  patients  was  two  years  of  age,  another  three  years 
and  another  eleven  years.  There  were  thirty-eight  cas.es 
from  fifteen  years  to  thirty;  nineteen  from  thirty  to  forty- 
five;  two  from  forty-five  to  sixty,  (one  aged  forty-eight  and 
the  other  fifty) ;  and  one  from  sixty  to  seventy-five,  (aged 
sixty-one). 

According  to  these  facts,  paronychia  is  rarely  met  with 
in  patients  under  fifteen  years  of  age  or  over  forty-five; 
although  it  may  occur  at  the  age  of  two  or  three  years  or 
as  late  as  sixty-one.  The  favorite  age  appears  to  be  from 
fifteen  to  thirty,  at  which  period  nearly  two-thirds  of  the 
cases,  where  the  age  was  recorded,  were  observed.  It  is  by 
no  means  infrequent,  however,  from  thirty  to  forty-five,  at 
which  period  nearly  one-third  of  the  cases  have  occurred. 

In  sixty-three  cases  the  occupation  of  the  patient  was 
recorded. 

In  all  but  seven  of  these  cases,  the  patients  were  en- 
gaged in  occupations  requiring  considerable  manual  labor. 
These  seven  exceptions  were  a  clerk,  a  clergyman,  a  doctor,. 
a  student  of  medicine,  a  female  teacher  and  two  children 
at  school.  The  remaining  fifty-seven  were  mechanics, 
laborers  or  housemaids.  Of  these  there  were  twenty- 
three  housemaids,  five  housewives,  five  seamstresses  and 
two  laundresses.  Of  the  males  there  were  five  shoemakers, 
four  laborers,  two  sailors  and  two  blacksmiths. 

By  far  the  largest  number  of  cases  of  any  one  occupa- 
tion was  the  number  of  housemaids,  twenty-three  out  of 


ANALYSIS    OF    CASES    OF   PARONYCHIA  3 

sixty-three,  more  than  one-third  of  the  entire  number,  and 
nearly  five  times  the  number  of  cases  of  any  other  occupa- 
tion, five  being  the  next  highest  number. 

In  fifty-one  cases  the  probable  cause  of  the  affection 
was  recorded. 

Under  this  head  I  find  the  occupation  recorded  as  the 
cause  in  twenty-three  cases.  Of  these,  nine  were  accus- 
tomed to  housework,  scrubbing,  etc.  One  of  the  patients, 
a  shoemaker,  says  that  shoemakers  are  pecuHarly  hable  to 
paronychia  from  turning  boots  inside  out.  A  similar  state- 
ment was  made  by  another  patient,  who  said  that  lathers 
and  plasterers  were  liable  to  it,  from  driving  small  nails  and 
frequently  bruising  their  fingers. 

Five  cases  were  caused  by  bad  health;  two  cases  were 
the  result  of  slight  wounds;  two  cases  were  caused  by  sup- 
pressed menses.  These  were  of  the  first  variety,  par- 
onychia cutanea,  and  were  treated  with  nitrate  of  silver  and 
poultices.  One  case,  a  boy  three  years  old,  was  caused  by 
his  being  deprived  of  meat  under  the  impression  that  he 
would  thus  avoid  the  cholera.  He  had  been  accustomed 
to  meat  diet  and  ordinarily  was  healthy;  but  now  he  has  a 
paronychia  and  cankers  in  his  mouth  and  nose.  A  clergy- 
man brought  on  a  felon  by  rowing  a  boat;  a  school  girl,  by 
practicing  on  the  piano;  and  a  housemaid,  by  washing 
dishes.  One  case  occurred  after  an  attack  of  ship  fever. 
Another  case,  a  seamstress,  occurred  in  a  patient  of  a 
scrofulous  diathesis  who  had  an  anal  fistula. 

From  the  foregoing  facts  it  is  seen  that  the  causes  of 
paronychia  are  various.  The  most  frequent  causes,  how- 
ever, are  exposure  of  the  hands  to  hot  water,  as  in  washing 
dishes,  or  a  slight  hurt  or  bruise.  In  forty-one  cases  the 
causes  were  of  this  description.  More  rarely  the  cause  is 
general  or  constitutional.  In  ten  cases  the  causes  were  re- 
corded as  bad  health,  ship  fever,  suppressed  menses,  etc. 

Of  the  entire  number  of  cases  one  was  not  properly  a 
paronychia  but  was  a  fungus  at  the  root  of  the  nail;  eight 
were  of  the  first  variety,  paronychia  cutanea;  five  were  of 
the  first  and  second  variety,  cutanea  and  cellulosa;  and  the 
remaining  sixty-seven  were  of.  the  second,  third  and  fourth 
varieties,  cellulosa,  tendinosa  and  osteosa.  In  the  case  of 
the  fundus  at  the  root  of  the  nail  nothing  is  recorded  but 


4  ANALYSIS    OF    CASES    OF    PARONYCHIA 

that  on  the  twenty-first  day  the  fungus  was  the  size  of 
a  pea. 

The  cause  was  recorded  as  constitutional  in  three  of  the 
five  cases,  which  were  of  the  first  and  second  varieties  com- 
bined. There  was  no  record,  under  this  head,  in  the  re- 
maining two  cases.  In  three  of  these  cases  the  treatment 
was  merely  the  application  of  nitrate  of  silver;  one  case  dis- 
charged spontaneously  on  the  eighth  day,  but  the  inflam- 
mation extended  to  the  areolar  tissue,  pus  was  formed  and 
it  was  opened  on  the  fourteenth  day;  in  the  remaining  case 
there  was  no  record  under  the  head  of  treatment.  All  these 
cases  resulted  in  perfect  cures. 

Of  the  eight  cases  of  the  first  variety,  paronychia  cuta- 
nea, six  were  caused  by  slight  injuries  and  two  were  de- 
pendent upon  constitutional  causes.  Six  were  treated  with 
nitrate  of  silver  and  poultices;  one,  with  poultices  only; 
and  one  got  w-ell  spontaneously.  One,  however,  was 
opened  before  the  nitrate  of  silver  was  applied.  Four  of 
these  cases  resulted  in  perfect  cures,  one  of  them,  in  the 
loss  of  the  nail,  and  the  remaining  three  appear  to  have  been 
lost  sight  of. 

In  the  sixty-seven  cases  which  were  of  the  second,  third 
and  fourth  varieties,  I  shall  consider  only  one  feature  in  the 
treatment;  namely,  w^hether  it  w^as  opened  or  not  and 
how  long  after  the  onset  of  the  disease  before  it  was 
opened.  The  other  measures  of  treatment  were  so  imper- 
fectly recorded  that  their  consideration  would  be  of  little 
value. 

In  fifty-five  cases  the  results  w'ere  recorded.  Thirty- 
six  resulted  in  perfect  cures;  and  nineteen,  either  in  loss  of 
part  of  the  finger  or  in  anchylosis. 

Of  the  thirty-six  cases  twenty-nine  were  opened;  in  the 
remaining  seven  cases  there  was  no  record  under  this  head. 
In  twenty-seven  cases  pus  had  been  formed.  The  remain- 
ing nine  did  not  suppurate. 

Of  the  twenty-nine  cases  where  the  finger  was  laid  open, 
ten  were  opened  on  the  seventh  day.  Eight  of  these  had 
suppurated  and  tw-o  had  not.  Seven  were  opened  on  the 
tenth  day;  three  on  the  fourteenth  day;  two  on  the  thir- 
teenth day;  one  on  the  eighth  day;  one  on  the  eleventh  day; 
and  one  on  the  fifth  day.  All  of  these  had  suppurated. 
Two  were  opened  on  the  fourth  day,  one  having  suppurated 


ANALYSIS    OF   CASES    OF    PARONYCHIA  5 

and  one  not.  One  was  opened  on  the  third  day  and  one  on 
the  second  day,  neither  of  them  having  suppurated. 

In  the  nineteen  cases  where  the  cure  was  imperfect, 
twelve  were  opened  and  in  seven  there  was  no  record 
under  this  head.  One  was  opened  on  the  twenty-eighth 
day;  one  on  the  twentieth  day;  one  on  the  fifteenth  day; 
one  on  the  fourteenth  day;  two  on  the  seventh  day;  and  one 
on  the  fourth  day.  In  the  last  case  no  pus  was  found.  One 
case  discharged  spontaneously.  This  case  was  treated  by 
an  empiric,  who  was  prosecuted  and  mulcted  in  damages 
for  not  opening  the  finger.  The  case  resulted  in  a  loss  of 
the  entire  finger. 

From  the  results  of  these  fifty-five  cases  it  is  seen  that 
a  perfect  cure  may  be  expected  in  the  majority  of  cases. 
In  the  cases  which  resulted  in  perfect  cures  only  six  out 
of  twenty-nine  were  opened  after  the  tenth  day;  seven  were 
opened  on  the  tenth  day;  ten  on  the  seventh  day;  and  one 
was  opened  as  early  as  the  second  day,  before  pus  had  been 
formed.  None  were  opened  later  than  the  fourteenth  day. 
But  in  the  cases  where  the  cure  was  imperfect,  one  was  not 
opened  at  all;  seven  were  opened  from  the  fourteenth  to 
the  twenty-eighth  day;  two  only  were  opened  as  early  as 
the  seventh  day,  and  one  on  the  fourth  day. 

These  facts  show  the  importance  of  opening  the  finger 
at  least  as  early  as  the  tenth  day;  and  it  seems,  indeed,  to  be 
proper  to  do  so  as  soon  as  the  disease  becomes  established, 
even  before  pus  has  been  formed. 

INFLAMMATION   OF   THE   FINGER   OF   THE    SAME    CHARACTER 
AS    PARONYCHIA,    BUT    NOT    IN    THE    LAST    PHALANX 

Dr.  Hamilton  recorded  eighteen  cases  which  came 
under  this  head.  In  nearly  every  particular  they  are  the 
same  as  paronychia  proper;  but  as  the  number  of  these 
cases  is  large,  it  may  be  as  well  to  consider  them  by  them- 
selves. 

As  in  paronychia,  female  patients  predominate,  ten 
being  females  and  eight  males.  The  age  at  which  they 
seem  to  be  most  liable  to  the  affection  is  also  the  same.  No 
case  occurred  under  fifteen  years ;  twelve  cases  from  fifteen 
to  thirty;  three  from  thirty  to  forty-five;  two  at  thirty-two 
years;  and  one  at  thirty-seven.  No  cases  occurred  after 
the  age  of  thirty-seven. 


6  ANALYSIS    OF    CASES    OF    PARONYCHIA 

The  right  hand  was  affected  in  eight  out  of  ten  cases, 
where  the  hand  was  noted.  Out  of  thirteen  cases  the 
thumb  was  atTected  in  one  case;  the  first  finger  in  one  case; 
the  second  finger  in  six  cases;  the  third  finger  in  five  cases; 
but  in  no  case  was  the  fourth  finger  afifected.  Here  is  a 
diliference  from  paronychia,  w'here  the  thumb  and  first  fin- 
ger were  aft"ected  in  a  great  majority  of  cases.  I  can  see  no 
cause  for  this  difierence,  except,  perhaps,  that  the  causes 
which  produce  this  affection  appear  to  be  more  purely  acci- 
dental than  in  paronychia  and  not  so  much  due  to  the  oc- 
cupation of  the  patient;  and  that  the  last  phalanges  of  the 
thumb  and  forefinger  are  most  used,  not  the  entire  finger 
and  thumb,  while  the  other  phalanges  of  the  second  and 
third  fingers  are,  perhaps,  more  liable  to  accidental  injuries 
than  the  first  phalanx  of  the  thumb  or  the  first  or  second 
phalanges  of  the  forefinger. 

Of  sixteen  cases  the  first  phalanx  was  affected  in  four 
cases;  the  first  and  second  in  one  case;  the  second  in  five 
cases;  the  second  and  third  in  one  case;  and  the  meta- 
carpo-phalangeal  articulation  in  five  cases.  This  shows 
that  the  first  and  second  phalanges  are  about  equally 
liable  to  it;  and  also  the  metacarpo-phalangeal  articula- 
tion. 

As  regards  the  occupation  of  the  patients,  it  is  seen 
that  the  same  classes  of  society  are  affected  with  this  dis- 
ease as  those  affected  with  paronychia.  Here,  also,  house- 
maids and  housewives  predominate.  Of  seventeen  cases 
there  were  six  housemaids,  three  housewives,  two  sailors, 
tW'O  stone  cutters,  one  cabinet  maker,  one  male  cook,  one 
cooper  and  one  clergyman.  The  clergyman  is  the  one 
referred  to  in  the  cases  of  paronychia.  This  affection  oc- 
curred wath  the  paronychia  and  was  due  to  the  same 
cause;  namely,  rowing  a  boat. 

As  regards  the  causes  which  operated  to  produce  the 
disease,  of  ten  cases  where  the  causes  were  noted,  in  five 
the  occupation  was  recorded  as  the  cause.  These  five 
cases  embraced  four  housemaids  and  one  cabinet  maker. 
In  one  case  the  cause  was  a  slight  cut;  in  another  a 
slight  burn;  in  another  a  slight  bruise;  and  another  was 
caused  by  rowing  a  boat. 

Fourteen  cases  w^re  recorded  as  having  been  opened: 
two,  eight  days  after  the  beginning  of  the  disease;  five. 


ANALYSIS    OF    CASES    OF    PARONYCHIA  7 

seven  clays  after;  six,  five  days  after;  and  one,  three  days 
after. 

All  had  suppurated,  where  this  point  was  noted,  except 
one  case. 

Ten  cases  were  recorded  as  resulting  in  perfect  cures; 
and  one,  as  resulting  in  a  permanent  contraction  of  the  fin- 
ger. This  last  case  was  opened  on  the  seventh  day;  but 
afterward  the  finger  became  very  much  inflamed  and  suppu- 
rated profusely. 

This  afifection  differs  from  paronychia  only  in  the  situ- 
ation of  the  inflammation.  It  is  of  precisely  the  same  char- 
acter and  demands  the  same  treatment;  namely,  when  the 
inflammation  is  not  superficial,  an  early  and  free  opening. 
It  appears,  however,  to  be  rather  less  formidable  than  par- 
onychia, and  the  results  usually  are  much  more  favorable. 
In  only  one  of  eleven  cases  of  inflammation  of  the  first  or 
•second  phalanges  was  the  cure  imperfect;  and  in  this  case 
the  inflammation  ran  very  high  after  the  finger  was  opened, 
and  resulted  in  permanent  contraction  of  the  flexors;  while 
in  nineteen  out  of  fifty-five  cases  of  paronychia  proper,  the 
cure  was  imperfect,  and  in  some  of  these  cases  the  last  pha- 
lanx, or  even  more  of  the  finger,  was  lost.  Dr.  Hamilton 
informs  me,  however,  that  in  two  or  three  cases,  not  record- 
ed, he  has  seen  an  entire  phalanx  destroyed  by  necrosis. 

PARONYCHIA    MALIGNA 

I  have  records  of  seven  cases  of  paronychia  maligna. 
Six  of  these  cases  were  recorded  by  Dr.  Hamilton,  and  one 
case  I  recorded  at  the  clinical  lectures  by  Prof.  Gross,  of 
the  University  of  Louisville. 

Case  I. — Joseph  Carnin,  aged  nine  years ;  admitted  to  the  Buf- 
falo Hospital  of  the  Sisters  of  Charity,  Oct.  19,  1848.  Habit  scrofu- 
lous; the  extremity  of  the  great  toe  of  the  left  foot  was  swollen, 
red  and  sHghtly  tender ;  the  nail  was  black,  rotten  as  pasteboard, 
and  stood  directly  up  from  the  matrix.  This  has  been  his  condi- 
tion for  about  a  year. 

A  bread  and  water  poultice  was  applied  for  the  first  twenty- 
four  hours,  and  from  this  time  ung.  hyd.  rub.  or  the  ung.  hyd.  nit. 
was  applied  daily  to  the  foot.  The  diet  was  generous  and  he  was 
allowed  occasional  exercise.  Under  this  treatment  the  malady 
gradually  disappeared,  the  cure  being  accomplished  in  about  three 
months. 

Case  II. — Geo.  Vangu,  aged  seven  years.  He  had  scarlatina 
six  months  ago  and  was  very  ill  but  now  looks  healthy.     The  par- 


8  ANALYSIS   OF   CASES   OF   PARONYCHIA 

onychia  began  soon  after  his  recovery  from  scarlatina.  The  nail  is. 
black  and  rotten ;  the  affection  is  seated  on  the  second  finger  of  the 
right  hand.  Cause,  constitutional  and  local.  Treatment  has  been 
poultices,  unguents,  caustics,  etc.,  etc.  Corrosive  sublimate  wash 
increased  the  irritation;  poultices  gave  most  relief.  Result  is  un- 
known. 

Case  III. — Thomas  O'Connor,  aged  six  years.  Five  weeks  ago. 
he  split  the  nail  of  his  third  finger ;  one  week  since,  he  bruised  it. 
It  has  been  treated  with  poultices.  The  nail  became  black  and  fell 
off  but  was  reproduced,  and  of  the  same  character  as  before,  black 
and  rotten.  In  this  condition  the  finger  remained  many  months, 
under  different  plans  of  treatment.  Soothing  poultices  gave  most 
relief,  especially  when  combined  with  tonics  and  outdoor  exercise. 
He  was  eventually  cured. 

Case  IV. — Henry  W.  Putnam,  aged  nine  years.  Disease  af- 
fects the  thumb.  Cause,  constitutional  and  local.  As  regards  treat- 
ment, almost  everything  which  has  been  recommended  was  tried. 
Six  nails  have  fallen  off  successively  since  the  disease  began.  The 
end  of  thumb  is  flat  and  the  sides  are  puffed  out  and  of  a  purplish 
red  color ;  the  lower  half  of  nail  is  black  and  rotten ;  there  is  ulcera- 
tion under  the  nail;  the  parts  in  the  vicinity  are  red  and  puffy. 
The  result  in  this  case  was  a  cure. 

Case  V. — Williams,  male,  aged  five  years.  Cause,  probably  con- 
stitutional. He  was  apparently  in  good  health  but  had  slight  erup- 
tions on  various  parts  of  his  body.  It  has  been  treated  with  caustics, 
arsenic,  corrosive  sublimate,  poultices,  tonics,  hyd.  chlor.  mite,  etc.,. 
etc.  The  ulceration  did  not  cease  when  the  matrix  of  the  nail  was 
gone.  Arg.  nit.  in  substance,  was  first  applied ;  but  this  only  in- 
creased the  irritation ;  hyd.  chlo.  corros.  was  then  applied,  with  the 
same  result.  The  end  of  the  thumb  was  then  shaved  off  but  the 
ulceration  attacked  the  stump,  and  it  was  finally  necessary  to  ampu- 
tate the  last  phalanx,  when  the  wound  slowly  healed. 

Case  VI. — Wm.  Fitzgerald,  aged  eight  years.  He  has  parony- 
chia maligna  affecting  the  second  finger  of  the  right  hand.  Cause, 
constitutional  and  local.  He  ran  a  sliver  of  wood  under  the  nail 
four  months  ago.  It  has  been  poulticed  occasionally.  The  finger 
presents  the  usual  appearance  except  that  the  nail  is  not  blackened. 
He  has  a  scrofulous  ulceration  and  his  mother  is  scrofulous.  The 
poultices,  with  good  diet  and  cleanliness,  had  the  best  effect.  This- 
case  was  cured  after  several  months. 

Case  VII. — Catharine  Hynes,  aged  nine  years,  has  paronychia 
maligna  affecting  the  great  toe  of  the  left  foot.  Cause,  constitu- 
tional and  local.  She  has  a  scrofulous  appearance  and  received  a 
severe  contusion  upon  the  toe.  The  nail  was  removed  by  Prof. 
Gross,  and  the  toe  has  the  characteristic  shovel  shaped  appearance. 
Treatment  was  the  local  application  of  blue  wash,  and  slight  mer- 
curialization. 

I  saw  the  case  some  days  after  and  it  was  progressing  favor- 
ably. 

This  case  I  saw  at  the  Louisville  Marine  Hospital,  in  1854.  It 
was  treated  by  Prof.  Gross. 


ANALYSIS    OF    CASES    OF    PARONYCHIA  9 

Paronychia  maligna,  according  to  these  observations,  is 
a  disease  pecuHar  to  children.  Of  the  foregoing  cases  none 
were  more  than  nine  years  of  age.  Three  cases  were  nine 
years  of  age,  and  in  one  case  the  age  was  eight  years. 
There  was  one  case  of  seven  years;  one  case  of  six  years; 
and  one  case  of  five  years  of  age.  There  were  no  cases  of 
less  than  five  years  of  age. 

All  the  cases  recorded  by  Dr.  Hamilton  were  males; 
and  the  single  case  which  was  seen  by  myself  was  a  female. 
This  shows  a  very  great  predominance  of  males. 

The  affected  hand  or  foot  was  not  noted  in  a  suf^cient 
number  of  cases  to  make  its  consideration  of  value. 

The  great  toe  was  affected  in  two  cases;  the  thumb  in 
two  cases;  the  second  finger  in  two  cases;  and  the  third  fin- 
ger in  one  case.  Thus  the  hand  was  affected  in  five  cases, 
and  the  foot  in  only  two;  showing  that  the  disease  was 
much  more  frequently  seated  in  the  finger  or  thumb  than 
in  the  great  toe,  which  I  believe  is  contrary  to  the  general 
opinion.  When  the  foot  was  affected  it  was  always  in  the 
great  toe;  but  in  the  cases  where  the  hand  was  affected  it 
attacked  the  thumb  or  second  and  third  finger.  No  cases 
were  recorded  of  the  disease  seated  in  the  first  or  fourth 
finger. 

In  all  these  cases  but  one  the  cause  appeared  to  be 
either  purely  constitutional  or  at  least  partially  so.  In  one 
case,  however,  the  cause  was  apparently  local  (Case  IV, 
H.  W.  Putnam),  though  the  progress  of  the  disease  shows 
that  the  system  was  somewhat  at  fault.  In  three  cases  the 
cause  was  pvtrely  constitutional;  and  in  three  cases  it  was 
constitutional  and  local. 

Such  a  variety  of  treatment  has  been  practiced  in  these 
cases  that  its  consideration,  with  reference  to  results,  is  of 
little  value.  Tonics,  cleanliness  and  soothing  applications 
appear  to  have  had  the  best  effect;  and  mild  mercurial  ap- 
plications were  used  with  advantage  in  two  cases  in  connec- 
tion with  outdoor  exercise,  tonics  and  poultices.  Caustics, 
where  they  have  been  used,  have  not  been  productive  of 
any  good  effects  but  appear  rather  to  have  aggravated  the 
disease. 

Four  cases  (I.  III.  IV.  and  VI.)  are  known  to  have  re- 
sulted in  perfect  cures.  In  three  cases  tonic  measures  and 
poultices  were  employed.     In  addition  to  these  measures, 


lo  ANALYSIS   OF   CASES    OF    PARONYCHIA 

in  one  case,  ung,  hyd.  rub.  dilutiim  was  used.  In  one  case 
(V.)  it  was  necessary  to  amputate  the  last  phalanx  of  the 
thumb.  In  one  case  (II.)  the  result  was  unknown.  I  saw 
Case  VII.  several  times  at  the  Louisville  Marine  Hospital. 
It  was  progressing  favorably  and  probably  resulted  in  a 
perfect  cure. 

From  these  facts  it  may  be  inferred,  that  although  the 
disease  is  likely  to  be  protracted  and  tedious,  yet  with 
proper  care  a  perfect  cure  is  to  be  expected.  Amputation 
of  the  affected  part  will  rarely  be  necessary. 


II 

PHENOMENA  OF  THE  CAPILLARY  CIRCU- 
LATION—AN INAUGURAL  DISSERTATION 
LAID  BEFORE  THE  FACULTY  OF  THE 
JEFFERSON  MEDICAL  COLLEGE  IN  FEB- 
RUARY,  1857 

Published  in  the  "  American  Journal  of  the  Medical  Sciences"  for  July,  1857. 

The  Statements  which  I  shall  make  from  my  own  ob- 
servation concerning  the  capillary  circulation  are  based 
upon  examinations  made  from  time  to  time  during  the  past 
summer,  eight  of  which  have  been  carefully  recorded.  The 
recorded  observations  were  made  on  the  web  of  the  frog, 
although  I  made  examinations  of  the  various  other  parts 
where  the  circulation  can  be  conveniently  exhibited,  to 
which  I  shall  refer. 

The  microscope  used  was  the  large  instrument  of 
Nachet;  and  unless  otherwise  stated,  with  a  magnifying 
power  of  165  diameters. 

I  shall  first  point  out  what  I  have  found  to  be  the 
most  convenient  methods  of  conducting  examinations  of 
the  circulation  in  the  frog,  then  proceed  to  describe  the 
various  phenomena  of  the  circulation  as  viewed  by  means 
of  the  microscope,  and  then  draw  my  deductions  from  these 
observations. 

The  parts  of  the  frog  which  I  have  subjected  to  exami- 
nation are  the  web  of  the  foot,  the  tongue,  the  peritoneum 
and  the  lungs.  All  parts  except  the  peritoneum  should  be 
examined  by  transmitted  light;  but  in  examining  the  cir- 
culation in  the  latter  situation  it  is  necessary  to.use  reflected 
hght. 

It  is  exceedingly  inconvenient  to  miake  observations 
while  the  frog  has  the  power  of  motion,  and  in  securing  it 
to  the  frog-plate  in  a  proper  position,  we  are  likely  to  inter- 
rupt or  modify  the  circulation  by  constricting  the  vessels 


12  THE    CAPILLARY    CIRCULATION 

with  the  Ijands  which  we  must  use.  Under  these  circum- 
stances medicated  solutions  can  not  conveniently  be  ap- 
plied to  the  entire  surface,  and  mechanical  or  chemical 
irritation  of  any  part  occasions  struggles  which  greatly 
increase  the  difficulty  of  the  experiment.  By  breaking  up 
the  medulla  oblongata,  or  even  the  posterior  part  of  the 
brain  (for  it  is  not  easy  to  invariably  reach  the  medulla 
without  some  practice),  one  is  enabled  to  observe  all  the 
phenomena  of  the  circulation  with  great  facility,  avoiding 
the  necessity  of  forcibly  retaining  the  frog  in  the  desired 
position,  with  the  consequent  liability  to  constriction  of  the 
vessels  and  shifting  of  the  field  of  observation.  I  shall  here- 
after refer  to  the  experiments  of  E.  Brown-Sequard,  of 
Paris,  and  two  of  my  recorded  examinations,  which  show 
that  observations  of  the  circulation  may  be  made  with  as 
much  accuracy  on  a  frog  after  the  medulla  has  been  de- 
stroyed as  though  it  had  not  been  subjected  to  the  opera- 
tion. The  operation  may  be  performed  by  introducing  a 
dissecting  needle  into  the  cranium,  a  line  or  two  behind  the 
eyes,  passing  it  backward  and  a  little  downward  to  the 
articulation  of  the  spine  with  the  skull,  and  then  thoroughly 
breaking  up  the  medulla.  The  web  of  the  foot  may  be 
examined  in  the  following  manner:  First  break  up  the  me- 
dulla oblongata  in  the  manner  just  described;  the  frog  will 
then  remain  perfectly  motionless  in  any  position.  The  w^eb 
may  be  stretched  over  the  opening  in  the  frog-plate  and 
secured  in  position  by  means  of  pins,  care  being  taken  not 
to  extend  the  web  too  forcibly,  and  to  put  no  pins  above 
the  foot,  but  nearly  at  the  extremities  of  the  toes,  as  in 
either  case  the  circulation  may  be  disturbed.  The  part 
should  then  be  moistened,  and  the  lenses  of  the  microscope 
protected  from  the  evaporation  by  a  glass  cover,  broken  to 
fit  between  the  toes. 

The  entire  surface  of  the  frog  should  be  moistened  from 
time  to  time  with  cool  water. 

The  magnifying  power  best  adapted  to  such  observa- 
tions, is  one  of  150  to  200  diameters. 

In  examining  the  tongue,  draw  it  out  of  the  mouth  and 
stretch  it  so  as  to  form  a  thin  transparent  film  by  means 
of  the  forceps  and  pins.  The  circulation  may  be  exhibited 
in  the  peritoneum  by  merely  exposing  that  membrane  and 
examining  it  wath  a  power  of  60  or  70  diameters  by  reflect- 


THE    CAPILLARY    CIRCULATION  13 

ed  light.  The  method  of  exhibiting  the  circulation  in  the 
lungs  of  the  frog  is  much  more  complicated  and  difficult 
than  either  of  the  preceding  experiments,  but  when  suc- 
cessfully performed,  it  is  one  of  the  most  beautiful  and  curi- 
ous demonstrations  in  the  whole  range  of  microscopic 
work. 

Dr.  Robert  Willis,  in  his  edition  of  "  Wagner's  Physiol- 
ogy," refers  to  the  appearances  of  the  pulmonary  circula- 
tion in  the  water  newt.  He  directs  that  the  newt  be  stran- 
gled after  an  inspiration.  "  The  abdomen  is  then  to  be  laid 
open,  and  the  entire  animal,  being  held  in  the  hands,  is 
placed  upon  a  glass  plate  as  a  '  porte-objet,'  and  one  of  the 
lungs  brought  into  the  field  of  view."  He  observes,  how- 
ever, that  the  circulation  lasts  but  a  short  time.  The  frog 
appears  to  me  to  be  a  much  better  subject  for  this  experi- 
ment ;  and  as  I  have  never  seen  the  process  of  showing  the 
pulmonary  circulation  in  this  animal  detailed  in  the  books, 
I  shall  describe  it  with  some  minuteness  as  practised  by 
Prof.  John  C.  Dalton,  of  Xew  York,  and  as  repeated  fre- 
quently by  myself. 

In  undertaking  it,  a  large  sized  frog  should  be  selected. 
After  having  broken  up  the  medulla  oblongata,  a  ligature 
is  to  be  placed  around  the  larynx  in  the  following  manner: 
The  mouth  being  widely  opened,  the  larynx  is  seen  just  in 
front  of  the  oesophagus.  A  ligature  is  now  carried  just 
under  the  mucous  membrane  by  means  of  a  small  curved 
needle.  This  is  effected  by  making  four  or  five  stitches, 
the  needle  being  introduced  at  the  point  where  it  came  out 
at  each  preceding  stitch,  so  that  the  ligature  shall  smoothly 
encircle  the  larynx  and  its  extremities  emerge  at  the  same 
point.  This  being  done,  a  small  blowpipe  is  introduced 
into  the  windpipe  and  the  ligature  is  held  in  readiness  to  be 
drawn  tight  by  an  assistant  when  required.  The  lungs 
must  now  be  moderately  distended  and  the  ligature  tight- 
ened, at  the  same  time  removing  the  blowpipe.  If  the  side 
is  now  carefully  opened  the  lung  will  protrude  and  may 
be  examined  by  transmitted  light. 

It  is  very  much  more  difficult  to  exhibit  the  circulation 
in  the  lungs  than  in  any  other  part.  The  chief  difficulties 
to  be  encountered  are  the  following:  First,  it  is  no  easy 
matter  to  fix  the  ligature  properly  around  the  larynx;  but 
when  this  has  been  done,  if  the  lungs  are  distended  too 


14  THE   CAPILLARY   CIRCULATION 

forciljly.  they  will  either  burst  or  the  circulation  will  be 
greatly  impeded;  and  if  not  distended  sufficiently,  they  will 
not  protrude  when  the  side  is  opened.  There  is,  also,  always 
some  difficulty  in  introducing  the  blowpipe,  and  its  delicate 
orifice  is  often  occluded  by  the  secretion  of  the  part.  When 
successful,  however,  in  exhibiting  the  circulation  in  the 
lungs,  the  capillaries  are  seen  encircling  the  air-cells,  which 
are  quite  large  in  the  frog.  This  is  an  extremely  beautiful 
and  interesting  sight — but  more  as  a  scientific  curiosity 
than  as  a  field  for  useful  investigation.  It  was  observed  by 
Dr.  Willis,  and  confirmed  by  Wagner  and  Gluge,  that  the 
transparent  plasma  which  is  found  occupying  the  space  next 
to  the  walls  of  the  capillaries  in  most  situations,  while  the 
blood-disks  occupy  the  centre,  constituting  the  still  layer 
of  Kirkes,  is  not  observed  in  the  capillaries  of  the  lungs; 
in  other  words,  the  vessels  are  crowded  to  their  very  walls 
with  corpuscles. 

For  this  remarkable  deviation  from  a  general  law  they 
ofifer  no  explanation. 

I  have  never  observed  this  peculiarity,  as  my  attention 
was  not  directed  to  it  when  examining  the  pulmonary  cir- 
culation. Those  who  believe  that  the  heart  is  solely  in- 
strumental in  propelling  blood  through  the  capillaries 
would  not  be  able  to  account  for  this  phenomenon;  but 
it  seems  to  me  it  can  be  explained  in  the  following  manner: 
The  blood  circulating  in  the  systemic  capillaries  nourishes 
the  tissues  by  the  liquor  sanguinis,  and  thus  the  attract- 
ive vital  force  operates  on  this  constituent.  The  plasma 
then  is  nearest  the  tissues  and  next  the  walls  of  the  vessels; 
but  the  pulmonary  capillaries  are  for  the  aeration  of  the 
blood,  a  process  which  is  effected  by  the  globules  and  not 
by  the  plasma,  since  the  great  mass  of  blood  is  not  sent  to 
the  lungs  for  purposes  of  nutrition,  but  for  aeration;  hence, 
the  globules,  which  here  feel  the  force  of  attraction  for  oxy- 
gen, occupy  the  space  next  the  walls  of  the  vessels. 

Taking  the  view  which  I  do  of  the  causes  of  the  capil- 
lary circulation,  this  explanation  is  satisfactory. 

Before  proceeding  to  describe  minutely  the  phenomena 
of  the  capillary  circulation,  I  shall  briefly  consider  the  ana- 
tomical structure  of  the  capillaries  and  of  the  blood. 

Ch.  Robin  recognizes  three  varieties  of  capillaries.  The 
first  variety  is  -j-sVo    to  -g-j-Q    of  an  inch  in  diameter,  and 


THE   CAPILLARY    CIRCULATION  15 

is  composed  of  a  transparent  homogeneous  membrane, 
Tswo  of  ai''  iiich  in  thickness,  with  nuclei,  and  sometimes 
nucleoli,  projecting  into  the  calibre  of  the  vessel.  The  nu- 
clei are  oval,  with  their  long  diameter  in  the  direction 
of  the  vessel.  These  are  embraced  under  the  head  of  the 
"  true  capillaries  "  of  Prof.  Kolliker. 

The  second  variety,  M.  Robin  describes  as  having  two 
coats:  the  membrane  with  the  longitudinal  nuclei  of  the 
first  variety,  and  investing  it,  a  second  membrane  with 
transverse  nuclei.  The  diameter  of  the  second  variety 
varies  between  -^^  and  ^^  of  an  inch.  This  variety  also 
probably  comes  under  the  head  of  the  "  true  capillaries  " 
as  described  by  Kolliker,  though  he  does  not  mention  the 
second  investing  membrane. 

The  third  variety,  M.  Robin  calls  venules  and  arteri- 
oles; Kolliker,  venous  and  arterial  transitionary  vessels. 
Their  diameter  is  -gV  to  iV  of  an  inch,  and  they  have 
added  to  the  two  coats  of  the  second  variety  a  third  coat  of 
areolar  tissue.  It  seems  to  me  most  convenient  and  proper 
to  consider  the  first  tw-o  varieties  of  M.  Robin,  or  the  "  true 
capillaries  "  of  Prof.  Kolliker,  simply  as  capillaries  (their 
tunic  being  a  prolongation  of  the  inner  coat  of  the  arteries), 
and  the  third  variety  of  M.  Robin  as  venules  and  arterioles. 
One  may  easily  distinguish  the  arterioles  from  the  venules, 
by  noticing  that  the  arterioles  give  off  branches,  while  the 
venules  receive  them;  that  the  arterioles  diminish  in  size 
in  the  direction  of  the  current  of  blood,  while  the  venules 
increase  in  size. 

The  blood  consists  of  a  transparent  plasma  holding  two 
kinds  of  corpuscles  in  suspension,  called  the  red  and  white, 
or  colorless.  In  the  human  subject  the  red  corpuscles  are 
disks  like  pieces  of  coin,  but  thinner  in  the  centre  than  at 
the  edges.  They  have  no  nuclei,  though  the  difference  in 
thickness  causes  the  centre  to  appear  dark  when  the  edges 
are  in  focus.  They  are  j-gig-g-  of  an  inch  in  diameter.  The 
white  corpuscles  are  larger  than  the  red,  being  j-^\-^  of  an 
inch  in  diameter;  they  are  globular,  white  and  granular. 
If  water  is  applied  to  them  they  are  rendered  transparent, 
and  we  can  distinguish  a  nucleus.  They  are  much  less 
abundant  than  the  red  corpuscles.  In  the  frog,  the  red 
corpuscles  are  oval  and  large,  with  a  central  rounded  nu- 
cleus.    They  are  y^Vo-  o^  ^'"i  ^"^^'^  i"  their  long  diameter. 


i6  THE    CAPILLARY    CIRCULATION 

The  white  globules  are  smaller  and  proportionally  more 
abundant  than  in  man.  The  blood-disks  in  nearly  all  ani- 
ma  are  red  by  reflected  light,  but  of  a  pale  amber  color  by 
transmitted  light. 

In  a  paper  communicated  to  the  ''  Medical  Examiner," 
August,  1852,  by  E.  Brovvn-Sequard,  M.  D.,  of  Paris,  en- 
titled "  Experimental  Researches  applied  to  Physiology 
and  Pathology,"  I  find  some  very  interesting  observations 
on  the  effect,  or  more  properly  the  absence  of  effect  on  the 
capillary  circulation,  of  the  section  of  various  nerves.  This 
observer,  with  the  assistance  of  Dr.  Siebert,  found,  "  after 
the  section  of  all  the  nerves  (the  sympathetic  and  cerebro- 
spinal) in  the  legs  of  a  number  of  frogs,  that  there  was  no 
appearance  of  trouble  in  the  capillary  circulation,  either  in 
one  hour  or  three  or  four  days  after  the  division  of  the 
nerves."  He  concludes  from  another  experiment  that  the 
nervous  action  (that  of  the  sympathetic  as  well  as  the  cere- 
bro-spinal  nerves)  is  not  necessary  for  the  change  of  col- 
or of  the  blood  in  the  capillaries.  It  is  proved  by  this  ex- 
periment that  the  capillary  circulation  is  not  immediately 
dependent  in  any  measure  on  nervous  influence. 

A  curious  fact  has  been  observed  by  Bernard;  viz.,  that 
after  a  section  of  the  sympathetic  in  the  neck,  the  corre- 
sponding side  of  the  face,  and  more  particularly  the  ear,  be- 
comes warmer  and  more  sensiti\-e  than  the  other  side.  The 
bloodvessels  appear  more  abundant  than  before  and  are 
enlarged.  Brown-Sequard  has  repeated  this  experiment 
and  concludes  that  the  increase  in  temperature  and  sensi- 
bility is  due  merely  to  passive  dilatation  of  the  vessels  from 
paralysis  of  their  coats  and  consequent  congestion.  I  have 
myself  seen  the  experiment  performed  by  Prof.  Dalton,  of 
New  York,  and  concur  with  him  in  the  opinion  that  the 
increase  in  temperature  and  sensibility  is  due  rather  to  an 
exaggeration  of  the  nutrition  of  the  parts;  for  specimens 
of  blood  drawn  from  the  two  ears  have  been  compared, 
and  there  has  been  found  a  marked  difference  in  their  actual 
chemical  composition. 

These  considerations  are  interesting  in  connection  with 
animal  heat  as  produced  by  the  molecular  changes  in  the 
various  tissues,  and  appear,  also,  to  bear  in  some  measure 
on  the  subject  of  the  capillary  circulation. 

I  shall  hereafter  take  the  ground  that  the  capillary  cir- 


THE    CAPILLARY    CIRCULATION  17 

dilation  is  in  a  great  measure  dependent  upon  an  attrac- 
tion of  a  chemico-vital  character  between  the  tissues  and 
the  nutrient  fluid. 

Now,  if  the  nutrition  of  the  part  is  augmented,  the  con- 
gestion is  due  to  the  greater  attraction  of  the  tissues  for  the 
blood,  the  capillaries  being  first  affected  by  its  influence. 
The  nutrition  is  affected,  because  the  blood  actually  under- 
goes greater  changes  than  on  the  other  side.  The  capil- 
lary circulation,  then,  in  this  case  seems  clearly  to  be  in  a 
measure  dependent  on  the  process  of  molecular  regenera- 
tion and  disintegration.  There  is  no  new  action  induced 
in  the  part,  but  simply  an  augmentation  of  the  usual  pro- 
cesses; and  if  this  is  so,  a  cause  of  the  capillary  circulation 
is  a  chemico-vital  attraction  of  the  tissues  for  the  blood. 
The  fact  that  there  can  be  a  greater  supply  of  blood,  cir- 
culating with  greater  force,  on  one  side  of  the  body  than 
in  the  corresponding  part  on  the  other  side,  seems  to  me 
an  insuperable  objection  to  the  idea  that  the  heart  alone 
circulates  the  blood  in  the  capillaries;  but  I  have  antici- 
pated, in  some  degree,  the  points  which  I  shall  hereafter 
consider  more  fully. 

When  I  began  to  describe  the  manner  of  making  ob- 
servations on  the  capillary  circulation  in  various  parts,  I 
assumed  that  destruction  of  the  medulla  oblongata  had  no 
appreciable  effect  on  the  capillaries.  Brown-Sequard  has 
demonstrated  by  experiment,  that  frogs  are  able  to  live 
perfectly  well  for  three  or  four  months  after  extirpation  of 
the  medulla,  and  that  all  the  functions,  except  pulmonary 
respiration,  go  on  apparently  as  usual. 

Before  I  met  with  these  observations,  I  made  two  ex- 
periments with  reference  to  the  reliability  of  observations 
made  on  a  frog  after  breaking  up  the  medulla  or  the  pos- 
terior part  of  the  brain. 

In  my  first  experiment  the  posterior  part  of  the  brain 
was  broken  up  in  an  unsuccessful  attempt  to  reach  the 
medulla. 

Observation  I. — The  circulation  was  observed  for  seven  hours 
and  was  but  slightly  retarded  when  the  experiment  was  concluded. 
For  the  first  two  hours  the  circulation  appeared  as  usual.  I  have 
made  many  unrecorded  observations  on  this  point  and  have  always 
arrived  at  the  same  result :  I  have  introduced  a  dissecting  needle 
at  the  back  of  the  head,  sometimes  reaching  the  medulla  and  some- 
2 


i8  THE   CAPILLARY   CIRCULATION 

times  not,  but  always  rendering  the  frog  perfectly  quiet  and  man- 
ageable;  and  I  have  been  unable  to  discover  any  effects  upon  the 
circulation  or  the  phenomena  produced  by  irritants. 

After  making  this  experiment  I  made  several  dissec- 
tions so  as  to  be  able  to  reach  the  medulla  oblongata  with 
certainty,  and  succeeded  in  destroying  the  medulla  in  the 
following  observations: 

Observation  II. — I  examined  the  circulation  for  five  hours 
M^ith  the  same  results  as  in  the  preceding  experiment.  There  was 
no  alteration  from  the  appearances  of  the  circulation  in  the  unin- 
jured frog,  at  least  for  the  first  two  or  three  hours. 

From  these  observations  added  to  my  unrecorded  ex- 
periments I  have  no  hesitation  in  saying  that  observations- 
on  frogs  after  breaking  up  the  medulla  oblongata  or  the 
posterior  part  of  the  brain  are  quite  as  valuable  as  those 
made  on  uninjured  frogs;  therefore  all  the  subsequent  ob- 
servations were  made  after  breaking  up  the  medulla,  un- 
less otherwise  stated. 

Dr.  Wilson  Philip  made  an  experiment  which  is  inter- 
esting, though  not  throwing  any  light  upon  the  causes  of 
the  capillary  circulation.  "  While  Dr.  Hastings  was  observ- 
ing the  circulation,  he  crushed  the  brain  by  the  blow  of  a 
hammer.  The  vessels  of  the  web  instantly  lost  their  power, 
the  circulation  ceasing;  an  effect  which  we  have  seen  can- 
not arise  from  the  ceasing  of  the  action  of  the  heart.  (Dr. 
Philip  here  refers  to  experiments  by  which  it  is  ascer- 
tained that  the  blood  will  circulate  for  several  minutes 
after  the  interruption  of  the  heart-action.)  In  a  short  time 
the  blood  began  to  move,  but  with  less  force."  I  may 
here  add  the  notes  of  a  similar  experiment  performed  by 
myself: 

Observation  III. — The  brain  of  the  frog  was  crushed  while 
Prof.  Flint  was  examining  the  circulation,  which  was  brisk  and 
regular ;  the  motion  instantly  ceased,  but  began  again  in  a  few  sec- 
onds, though  it  proceeded  more  slowly.  This  observation  in  every 
respect  confirms  that  of  Dr.  Philip. 

This,  as  I  have  before  remarked,  cannot  be  thought  to 
show  that  the  capillary  circulation  is  dependent  upon  nerv- 
ous influence,  but  merely  that  a  violent  shock  is  able  to 
arrest  momentarily  all  the  vital  functions.  In  several  of  my 
observations,  I  have  minutely  recorded  the  appearances  of 


THE    CAPILLARY   CIRCULATION  19 

the  capillary  circulation  and  have  noticed  the   following 
phenomena : 

Observation  IV. — I  examined  the  web  of  a  young  frog. 

From  a  careful  and  prolonged  examination,  it  is  evident  that 
there  is  a  difference  between  the  modes  of  circulation  in  the  arteri- 
oles and  the  venules.  The  blood  moves  more  freely  in  the  former 
and  the  motion  appears  to  be  dependent  on  an  attractive  force. 
This  is  not  so  evident,  however,  here  as  in  the  capillaries;  there 
the  blood  shoots  off  to  different  parts  of  the  tissues  in  a  manner 
which  cannot  be  dependent  upon  a  "  vis  a  tergo."  It  also  moves 
much  more  rapidly  in  some  of  the  capillaries  than  in  others,  the 
velocity  varying  in  the  same  vessel  at  different  times.  In  the 
venules,  the  movement  is  more  sluggish,  the  globules  apparently 
crowding  each  other  along,  and  on  careful  examination  making  a 
decided  contrast  to  the  movement  in  the  arterioles.  The  number 
of  colorless  globules  is  greater  in  the  venules ;  they  adhere  to  the 
walls  of  the  vessels  and  appear  to  be  pushed  along  by  the  central 
mass,  moving  very  much  more  slowly  and  occasionally  remaining 
stationary  for  a  time. 

Observation  V. — In  this  observation,  the  same  points  attracted 
attention  as  in  the  preceding  one,  and  in  addition,  the  following 
phenomena  were  noted : 

A  small  transverse  capillary,  admitting  but  a  single  globule  at 
a  time,  was  abruptly  bent  at  a  certain  point.  The  globules  passed 
along  in  single  file,  irregularly  isolated  from  each  other,  and  were 
bent  nearly  double  in  passing  the  sudden  turn  in  the  vessel.  This 
caused  the  globules  to  present  a  singular  appearance  at  this  point ; 
they  seemed  to  move  by  volition,  like  animate  beings.  The  motion 
of  the  globules  under  the  above  circumstances  seemed  to  indicate 
an  attractive  force. 

In  several  instances  the  walls  of  the  vessels  were  distinctly 
seen ;  they  were  perfectly  motionless,  evidently  taking  no  active 
part  in  the  circulation.  The  darting  of  single  globules  through 
small  vessels,  at  a  velocity  greater  than  the  velocity  of  the  circu- 
lation in  the  vessel  from  which  they  branched,  was  repeatedly  noted. 

Observation  VI. — The  points  noticed  in  Observation  IV  were 
here  confirmed.  I  was  forcibly  struck  with  the  great  difference 
in  the  velocity  of  the  circulation  in  different  parts  of  the  field,  both 
in  vessels  of  the  same  size  and  of  unequal  sizes.  I  also  remarked 
a  difference  of  velocity  in  the  same  vessels,  especially  capillaries, 
at  different  times. 

An  attractive  force  is  evident;  and  a  certain  condition 
of  the  disks  is  necessary  in  order  that  the  force  should 
operate.  This  condition,  it  may  be  presumed,  is  brought 
about  by  respiration. 

The  appearances  of  the  capillary  circulation  in  the  web 
of  the  foot  may  be  described  as  follows: 

When  the  web  is  subjected  to  examination  in  the  man- 


20  THE   CAPILLARY   CIRCULATION 

ner  already  described,  there  are  vessels  of  various  sizes  in  the 
field,  consisting  of  arterioles  and  venules,  wdiich  vary  most 
in  their  diameters,  and  the  true  capillaries  which  are  all 
of  nearly  equal  diameters.  The  blood  is  seen  coursing 
along  these  vessels  with  great  rapidity,  especially  in  the 
arterioles,  where  we  may  observe  a  slight  pulsatory  move- 
ment. 

In  the  arterioles,  blood  moves  with  unvarying  rapidity 
as  a  general  rule;  and  here  especially  we  notice  a  space  next 
the  walls  of  the  vessels,  which  is  not  occupied  by  the  red 
globules,  but  along  which  the  colorless  globules  move  at 
a  diminished  rate,  appearing  to  have  a  tendency  to  adhere 
to  the  walls  of  the  vessels,  and  sometimes  even  remaining 
entirely  stationary  for  a  time,  to  be  pushed  along  again  by 
the  central  mass.  This  constitutes  the  "  still  layer  "  of 
Kirkes. 

The  white  or  colorless  corpuscles  are  much  fewer  than 
the  red  and  they  move  at  least  ten  or  twelve  times  more 
slowly  than  the  central  mass.  On  careful  examination  I 
have  been  able  to  note  a  decided  difference  between  the 
circulation  in  the  arterioles  and  the  venules.  In  the  latter 
the  movement  is  not  so  rapid,  the  globules  appearing  to 
be  impelled  more  by  a  "  vis  a  tergo  "  and  to  feel  less  the 
"  vis  a  fronte,"  wdiich  seems  to  operate  in  the  arterioles. 
The  comparative  number  of  the  white  corpuscles  is  greater, 
but  the  "  still  layer  "  appears  to  occupy  a  smaller  propor- 
tion of  the  calibre  of  the  vessel. 

In  the  true  capillaries  the  movements  are  less  regular 
and  apparently  are  dependent  in  a  great  measure  on  a  force 
which  acts  directly  upon  them;  the  "capillary  power,"  as 
it  is  designated  by  Dr.  Carpenter.  This  will  be  more  fully 
touched  upon  presently  in  considering  the  causes  of  the 
capillary  circulation. 

In  the  true  capillaries  the  blood  moves  in  every  possi- 
ble direction,  at  different  rates  of  speed  in  different  vessels 
and  at  different  times  in  the  same  vessel.  In  one  instance 
I  remarked  a  capillary  branching  from  a  vessel  at  an  obtuse 
angle  (that  is,  turning  almost  directly  opposite  to  the  cur- 
rent in  the  main  vessel),  and  individual  globules  shooting 
through  it  with  great  rapidity.  In  many  instances,  I  ob- 
served a  complete  stasis  in  one  or  two  of  the  capillary  ves- 
sels, but  it  existed  only  for  a  moment  and  the  current  began 


THE   CAPILLARY   CIRCULATION  21 

again  with  its  original  vigor.  Dr.  Carpenter  has  remarked 
a  stasis  followed  by  a  current  in  an  opposite  direction. 

It  frequently  happens  that  a  globule  is  caught  at  the 
point  of  junction  of  two  vessels  and  remains  stationary  until 
it  is  carried  along  by  the  current  of  blood.  Globules  are 
frequently  bent  upon  themselves  as  they  pass  from  one  ves- 
sel to  another,  but  so  soon  as  the  cause  is  removed  they 
regain  their  original  conformation. 

The  walls  of  the  vessel  are  motionless,  and  they  do  not 
take  an  active  part  in  the  normal  circulation  as  was  sup- 
posed by  some  of  the  older  writers. 

Pigment-cells  are  observed  scattered  over  the  field, 
when  they,  are  very  abundant  obscuring  the  view  of  the 
circulation;  therefore  it  is  best  to  select  a  light  colored 
frog  for  demonstrations. 

The  pavement  variety  of  epithelium  may  also  be  seen. 

This  is  a  description  of  the  capillary  circulation  as  it  ap- 
peared to  me  under  the  most  favorable  circumstances: 
more  minute,  but  not  otherwise  differing  from  the  ordinary 
description  in  works  on  physiology. 

I  now  come  naturally  to  a  consideration  of  the  causes 
of  the  capillary  circulation.  I  say  causes,  because  I  shall 
take  the  ground  that  it  is  not  produced  by  a  single  cause; 
namely,  the  heart's  contraction,  as  was  supposed  by  the 
great  discoverer  of  the  circulation.  While  it  may  be  that 
the  action  of  the  heart  is  sufficient  to  propel  the  blood 
through  the  whole  round  of  the  circulation,  as  is  contended 
by  Magendie,  by  Dr.  Allen  Thompson,  in  the  "  Cyclopedia 
of  Anatomy  and  Physiology,"  Dr.  Kirkes  and  others,  I 
believe  that  there  are  other  causes  which  operate  and  are 
able  to  carry  on  the  circulation  unassisted,  as  was  the  case 
in  the  acardiac  foetus  of  Dr.  Houston,  reported  in  the 
"  Dublin  Medical  Journal,"  1837,  where,  of  course,  the  cir- 
culation was  stopped  at  the  birth  of  the  child  by  the  want 
of  due  aeration  of  the  blood. 

Harvey,  followed  by  Magendie,  Kirkes  and  other  emi- 
nent physiologists,  supposed  that  the  heart  was  alone  con- 
cerned in  the  production  of  the  circulation,  and  some  very 
striking  arguments  were  made  use  of  to  prove  it.  It  is 
found  that  under  the  most  favorable  circumstances  a  very 
inconsiderable  force  is  required  to  propel  a  bland  fluid  from 
the  arteries  through  the  capillaries  and  out  again  by  the 


22  THE    CAPILLARY    CIRCULATION 

veins.  The  pulsative  movements,  which  are  observed  un- 
der some  circumstances  in  the  capillaries,  is  also  brought 
forward  as  an  argument.  Dr.  Kirkes  dismisses  the  subject 
with  the  remark  that  "  there  is  no  need  of  an  hypothesis  of 
any  action  of  the  capillaries  for  regular  propulsion  of  the 
blood  through  them,  nor  is  it  probable  they  have  such  an 
office."  This  appears  to  me  a  most  unphiloso])hical  mode 
of  treating  a  very  important  subject.  The  circulation  of 
the  blood  is  a  process  immediately  necessary  to  existence; 
and  even  admitting  that  the  action  of  the  heart  is  quite 
capable  of  carrying  on  the  circulation,  it  would  not  be  out 
of  place  to  inquire  if  there  be  not  some  other  force  which 
also  operates  to  this  end,  and  can  take  on,  in  some  degree, 
the  function  of  circulating  the  blood,  should  the  heart  be- 
come W'Cakened  from  any  cause.  In  the  performance  of 
that  essentially  vital  function,  respiration,  we  commonly 
use  but  about  one-third  of  the  entire  capacity  of  the  lungs; 
and  though  the  lungs  seem  to  be  only  aerating  organs, 
they  divide  that  function  with  the  skin.  One  might  as  well 
say  that  as  the  diaphragm  is  sufficient  to  carry  on  respira- 
tion, there  is  no  need  of  supposing  that  there  are  any  other 
respiratory  muscles. 

There  are  several  phenomena  which  are  difficult  of  ex- 
planation on  the  theory  of  the  sole  action  of  the  heart  in 
producing  the  circulation.  In  the  first  place  it  is  difficult 
to  understand  how  the  heart  could  impel  the  blood  through 
the  second  set  of  the  capillaries  in  the  portal  system.  Then 
the  experiments  of  Dr.  Dowler  show  that  the  blood  prob- 
ably circulates  in  the  capillaries  in  patients  dead  from  yel- 
low fever,  after  the  heart's  action  has  ceased. 

In  the  frog,  Dr.  Carpenter  asserts,  and  I  have  myself 
seen  that  the  blood  will  circulate  in  the  capillaries  after 
complete  excision  of  the  heart.  Carpenter  also  mentions 
instances  wdiere  the  heart  has  suffered  such  a  degree  of 
fatty  degeneration  or  displacement  that  there  existed 
scarcely  a  trace  of  muscular  fibre,  and  the  circulation  must 
have  been  chiefly  dependent  on  the  "  capillary  power." 
Hassall  records  a  most  remarkable  phenomenon;  namely, 
the  continuance  of  circulation  in  a  portion  of  the  tongue 
which  had  been  entirely  detached  from  the  body.  He 
states  that  while  examining  the  tongue  of  a  frog,  a  small 
portion  w^as  torn  off,  which  he  placed  between  two  plates 


THE    CAPILLARY   CIRCULATION  23 

of  glass  and  was  astonished  to  see  the  circulation  continu- 
ing in  many  of  the  smaller  vessels  with  unabated  vigor. 
This  phenomenon  he  observed  for  several  hours,  in  con- 
nection with  several  medical  gentlemen ;  and  on  examining 
it  the  next  day,  preserving  it  under  water  in  the  interval, 
the  circulation  still  continued  to  some  extent.  This  seems 
almost  incredible;  but  coming  from  such  authority  the  fact 
can  not  be  doubted.  Hassall  appears  to  have  made  no  sub- 
sequent experiments  with  reference  to  this  point.  After 
seeing  this  statement,  I  made  two  or  three  experiments, 
and  once  saw  a  slight  movement  in  a  portion  of  the  tongue 
entirely  detached;  these  experiments  were  not  made,  how- 
ever, under  favorable  circumstances,  the  weather  being 
cold,  and  the  frog  in  a  state  of  torpor  until  partially  aroused 
by  immersion  in  tepid  water. 

A  case  is  mentioned  by  Dr.  Carpenter  of  an  acardiac 
foetus  which  was  subjected  to  examination  by  Dr.  Houston, 
where  the  organs  were  tolerably  well  developed,  with  the 
exception  of  the  heart,  and  the  circulation  could  be  ef- 
fected only  by  the  "  capillary  power."  The  cases  which  I 
have  described  are  amply  sufficient  to  disprove  the  theory 
that  the  heart  is  the  sole  cause  of  the  circulation.  In 
addition,  the  phenomena  of  inflammation  as  seen  under 
the  microscope;  the  normal  appearances  of  the  capillary 
circulation,  which  appear  to  the  eye  to  be  in  some  measure 
dependent  on  an  attraction  of  the  molecules  of  the  tissues 
for  the  blood;  the  experiment  of  the  section  of  the  sym- 
pathetic in  the  neck  of  the  rabbit,  which  I  have  previously 
noticed,  and  which  produced  an  augmentation  of  this  at- 
tractive force  in  the  corresponding  ear  and  side  of  the  face; 
and  comparison  with  the  circulation  in  some  aquatic  plants, 
which  is  not  dependent  upon  the  action  of  a  heart ;  all  these 
go  to  show  that  the  heart  alone  does  not  carry  on  the  cir- 
culation. 

Prof.  Draper,  of  the  University  of  New  York,  has  pro- 
posed a  theory  in  regard  to  the  circulation,  which  makes 
the  heart  of  minor  importance.  His  is  the  theory  of  capil- 
lary attraction  and  affinity.  He  starts  with  the  proposition 
that,  "  if  two  liquids  communicate  with  each  other  through 
a  capillary  tube,  for  the  substance  of  which  they  have  affini- 
ties of  different  intensities,  movement  will  ensue;  the  liquid 
having  the  highest  affinity  will  occupy  the  tube,  and  may 


24  THE    CAPILLARY    CIRCULATION 

even  drive  the  other  from  it;  the  same  effect  will  ensue  in  a 
porous  object."  He  believes  that  this  is  the  main  cause  of 
the  circulation;  namely,  an  affinity  between  the  blood  and 
the  tissues;  that  thus  the  blood  is  forced  into  the  veins;  and 
that  the  action  of  the  heart  is  limited  to  filling  the  arteries 
and  presenting  a  supply  of  blood  to  the  capillaries.  The 
blood  circulates  in  the  lungs  chiefly  on  account  of  its 
affinity  for  oxygen. 

This  theory  can  not  be  sustained.  The  heart  undoubted- 
ly has  a  much  more  important  office  in  the  production  of 
circulation.  When  a  small  artery  is  cut  the  blood  is  seen 
forcing  itself  in  a  jet  to  a  distance  of  several  feet;  and  this 
happens  after  it  had  entirely  lost  the  influence  of  the  capil- 
lary force.  The  illustration  of  Prof.  Dunglison;  namely, 
the  law  that  fluids  confined  in  tubes  will  rise  to  the  same 
level,  and  that  thus  the  blood  in  the  veins,  by  a  simple  hy- 
drostatic principle,  would  rise  as  high  as  the  right  auricle  in 
a  line  with  the  blood  in  the  left  ventricle,  shows  how  slisfht  a 
force  from  the  heart  would  be  propagated  through  the  cap- 
illaries to  the  veins  and  be  sufficient  to  return  the  blood. 

Dr.  Dowler,  of  New  Orleans,  believes  in  a  distinct  capil- 
lary action.  In  some  of  the  experiments  which  he  adduces 
in  support  of  his  position,  and  which  are  noticed  by  Prof. 
Dunglison  in  his  "  Human  Physiology,"  bodies  of  yellow 
fever  patients  were  carried  to  the  dissecting  room  a  few 
moments  after  death.  "  The  external  veins  sometimes  be- 
came distended,  and  when  punctured,  the  blood  flowed  in 
a  good  stream;  the  operation  of  bleeding  at  the  arm  was 
imitated,  and  as  the  muscles  were  moved,  the  blood  shot 
forth  for  some  distance."  Other  experiments  on  the  veins, 
of  a  similar  character,  are  recorded  by  him. 

These  observations  seem  to  show  that  there  is  some 
action  in  the  capillaries  after  death,  and  inferentially  during 
life,  which  is  independent  of  the  heart's  action.  The  entire 
emptying  of  the  arteries  after  death  cannot  be  satisfactorily 
explained  by  mere  contraction  of  the  vessels. 

What  causes  seem  to  operate  to  produce  the  capillary 
circulation,  judging  merely  from  the  appearances  under  the 
microscope?  In  the  observations  which  I  have  recorded 
on  this  point,  I  noted  an  irregularity  of  the  movement  in 
the  capillaries,  both  in  different  vessels  at  the  same  time 
and  in  the  same  vessel  at  different  times;  the  irregularity 


THE    CAPILLARY   CIRCULATION  25 

sometimes  amounting  to  entire  cessation  of  the  circulation 
in  a  single  vessel,  and  then  a  current  in  an  opposite  direc- 
tion; a  shooting  off  of  single  globules  through  vessels 
which  were  before  empty;  the  darting  of¥  of  globules 
through  capillary  branches  with  a  velocity  greater  than 
that  of  the  blood  in  the  main  vessel;  and  in  short,  all  the 
phenomena  which  are  presented  to  the  eye  seem  to  indi- 
cate that  there  is  an  attractive  force,  resident  in  the  solid 
particles,  which  operates  on  the  blood  in  the  capillaries. 

I  am  not  supposing  the  existence  of  a  force  with  the 
operation  of  which  physiologists  are  unacquainted.  The 
present  school  of  physiology  teaches  that  the  processes  of 
nutrition,  of  molecular  disintegration  and  of  secretion  are 
dependent  on  a  vital  force  resident  in  the  solid  particles  of 
the  organism  which  are  essentially  vitalized.  Inflamma- 
tion is  now  supposed  to  be  due  to  a  perversion  of  this  force. 

What  other  explanation  is  there  of  the  fact  that  every 
tissue  takes  from  the  mass  of  arterial  blood  the  substances 
which  are  required  for  its  nutrition?  The  blood  sent  to  the 
systemic  capillaries  by  the  heart  is  the  same  in  all  parts  of 
the  body;  but  when  the  great  change  which  is  effected  in 
the  capillaries  has  taken  place,  the  blood  which  has  thus 
been  rendered  venous  is  not  the  same  in  all  the  veins;  for 
example,  the  blood  in  the  renal  vein  is  almost  as  florid  as 
arterial  blood. 

The  existence  of  a  distinct  capillary  action  is  now  be- 
lieved by  the  highest  authorities.  Lehmann  believes  that 
a  chemico-vital  attraction  of  the  blood  for  the  tissues,  to- 
gether with  the  physical  capillary  attraction,  produces  the 
movement  of  the  blood  in  the  capillaries  and  forces  it  into 
the  veins.  Dr.  Carpenter  believes  that  there  exists  a  "  cap- 
illary power  "  which  is  superadded  to  the  force  of  the  heart. 
Prof.  Dunglison  teaches  that  there  is  an  independent  power 
resident  in  the  tissues  about  the  capillaries,  and  that,  "  by 
the  united  action  of  the  heart,  arteries  and  capillaries,  or 
intermediate  system  of  vessels,  the  blood  attains  the  veins." 
Even  those  who  recognize  the  heart  as  the  only  efficient 
organ  of  circulation  admit  that  the  capillaries  possess  a 
"distributive  force;"  that  is.  though  the  circulation  is 
effected  by  the  heart's  unassisted  action,  the  tissues  have 
an  attraction  or  affinity  for  the  blood,  which  distributes 
it  for  their  nutrition  to  each  and  every  part  of  the  body. 


26  THE   CAPILLARY   CIRCULATION 

Taking  into  consideration  everything  that  I  have  seen 
bearing  on  this  point,  it  seems  to  me  to  be  clearly  proved 
that  the  normal  capillary  circulation  is  dependent,  in  the 
hrst  place,  on  the  action  of  the  heart.  It  cannot  be  denied 
that  the  heart  has  a  considerable  share  in  producing  ca])- 
illary  circulation.  Taking  into  account  the  conditions  of 
the  blood  and  vessels,  apparently  a  slight  force  is  capable 
of  propelling  the  blood  through  the  capillary  system. 
When  a  small  artery  is  divided,  the  force  with  which  the 
blood  flows  out  is  considerable  and  appears  sufificient  to 
exert  a  decided  effect  on  the  motion  of  the  blood  in  the 
capillaries.  It  is  impossible  to  estimate  with  much  accura- 
cy the  proportional  influence  which  the  heart  has  in  produ- 
cing the  capillary  circulation.  The  vital  affinity  between 
the  tissues  and  the  blood,  which  I  suppose  to  be  the  other 
power  concerned  in  this  function,  never  ceases;  still,  as  the 
action  of  the  heart  is  frequently  much  interfered  with,  as 
in  cases  of  excessive  fatty  degeneration,  and  as  the  heart 
has  been  removed  from  the  frog,  the  capillary  circulation 
nevertheless  continuing,  I  cannot  think  that  its  power  is 
greater  than  the  active  force,  or  Carpenter's  "  capillary 
power,"  which  I  hold  to  be  essentially  concerned  in  the 
performance  of  this  function.  The  value  of  the  heart's  ac- 
tion is  also  variable,  both  in  different  individuals  and  in 
the  same  individual  at  different  times. 

The  only  other  force  which  has  any  share  in  the  produc- 
tion of  the  capillary  circulation,  except,  perhaps,  a  slight 
suction  force  from  the  veins,  is  the  "  capillary  power."  This 
seems  to  me  to  play  the  more  constant  and  effective  part. 
When  this  ceases  to  act  the  animal  dies  and  the  blood  re- 
fuses to  circulate  in  spite  of  the  heart.  This  is  the  great  vital 
force  of  nutrition  which  is  constantly  operating  and  which 
is  so  wonderful  and  inexplicable.  It  is  a  fact  that  there  is 
such  a  force  and  that  it  continually  acts;  but  what  it  con- 
sists of  or  what  is  its  essential  character  is  beyond  the  wis- 
dom of  man  to  explain.  It  is  life.  Finally,  the  following 
inquiry  suggests  itself:  What  conditions  are  necessary  to 
the  healthy  performance  of  the  capillary  circulation? 

First,  a  healthy  condition  of  the  vital  particles,  which 
is  produced  by  healthy  nutrition.  Second,  a  certain  con- 
dition of  the  blood,  which  is  produced  by  respiration. 

No  arguments  appear  to  be  necessary  to  prove  the 


THE    CAPILLARY    CIRCULATION  27 

former  statement;  but  I  have  made  experiments,  which  I 
shall  proceed  to  describe,  which  conclusively  establish  the 
second  point. 

The  following  experiment,  made  by  Dr.  J.  Reid,  and  re- 
ported in  the  "  Edinburgh  Medical  and  Surgical  Journal," 
April,  1 84 1,  is  quoted  by  Dr.  Carpenter: 

Dr.  Reid  found  that  when  the  ingress  of  air  through  the 
trachea  of  a  dog  was  prevented  and  asphyxia  was  pro- 
ceeding to  the  stage  of  insensil)ility,  the  pressure  in  the 
femoral  artery,  indicated  by  the  hemadynamometer,  was 
much  greater  than  usual. 

Upon  applying  a  similar  test  to  a  vein,  however,  the 
pressure  was  proportionally  diminished;  whence  it  became 
apparent  that  there  was  an  unusual  obstruction  to  the  pas- 
sage of  the  venous  blood  (the  blood  being  venous  in  the 
arteries)  in  the  systemic  capillaries. 

Before  seeing  an  account  of  this  experiment,  I  had  made 
the  following  observations,  carefully  recording  them,  with 
reference  to  the  same  point: 

Observation  VII. — The  medulla  of  a  medium-sized  frog  was 
broken  up  and  the  web  submitted  to  microscopic  examination.  The 
frog  was  bathed  with  sulphuric  ether,  care  being  taken  not  to  allow 
the  ether  to  touch  the  web  under  examination,  and  the  circulation 
was  watched  for  ten  minutes.  No  effect  could  be  discovered.  The 
object  of  this  experiment  was  to  determine  whether  the  phenomena 
in  the  succeeding  experiment  were  in  any  degree  dependent  on  the 
ether  which  is  contained  in  collodion. 

The  frog  was  then  painted  over  with  an  impermeable  coating 
of  collodion,  care  being  taken  as  before  not  to  touch  the  web.  The 
effect  on  the  circulation  was  immediate.  It  instantly  became  less 
rapid,  until  at  the  expiration  of  twenty  minutes  it  had  entirely 
ceased. 

The  smaller  vessels  were  the  first  to  become  affected,  the  larger 
arterioles  resisting  it  longest.  One  of  the  first  effects  was  a  pul- 
satile movement  in  vessels  where  the  blood  had  previously  flowed 
in  a  continuous  stream,  showing,  as  it  seemed,  that  the  attractive 
force  was  lost,  but  that  the  heart's  action  was  felt. 

The  fact  of  the  first  arrest  of  the  blood  in  the  capillaries  seemed 
to  indicate  that  the  blood  was  unfit  to  supply  the  wants  of  the  tis- 
sues, and  that  the  attractive  force  had  ceased  to  be  operative.  The 
arrest  of  the  circulation  was  steady,  and  at  the  expiration  of  twen- 
ty minutes  the  motion  had  entirely  ceased. 

The  entire  coating  of  collodion  was  then  instantly  peeled  off, 
and  the  effect  on  the  circulation  was  instantaneous.  Quite  a  rapid 
circulation  immediately  began,  but  it  soon  began  to  decline,  and  in 
twenty  minutes  had  almost  ceased.     The  heart  was  now  exposed 


28  THE    CAPILLARY   CIRCULATION 

and  found  contracting  regularly.  In  this  experiment  all  respiration 
was  abolished,  the  medulla  being  broken  up  and  an  impervious  coat- 
ing applied  to  the  entire  surface. 

Ohservation  VIII. — I  painted  a  frog  with  a  thick  coating  of 
collodion  without  destroying  the  medulla.  It  struggled  vigorously 
at  first,  but  soon  became  quiet  and  the  web  was  put  under  the  mi- 
croscope. 

The  circulation  was  affected  in  the  same  manner  as  in  the  pre- 
ceding experiment  and  entirely  ceased  in  twenty-five  minutes. 

During  the  first  few  minutes  the  nostrils  dilated  and  contracted 
rapidly  but  soon  became  motionless.  Care  was  taken  not  to  ob- 
struct the  nostrils  with  collodion,  although  it  was  applied  effectually 
to  all  other  parts  except  the  foot  under  observation. 

The  experiment  of  Dr.  Reid  proves  this  fact  inferen- 
tially;  namely,  that  the  blood,  deprived  of  oxygen,  as  in 
asphyxia,  is  retarded  in  the  systemic  capillaries;  but  the 
experiments  just  related  bring  the  processes  directly  under 
the  eye;  and  one  can  see  clearly  that  when  the  blood  is  not 
aerated  it  will  not  circulate,  although  the  heart  contracts; 
and  that  it  is  retarded  in  the  capillaries.  My  second  ex- 
periment demonstrated  the  comparatively  small  part  which 
the  lungs  of  the  frog  take  in  respiration;  the  blood  circu- 
lating in  the  frog,  in  which  the  pulmonary  respiration  was 
not  interfered  with,  only  five  minutes  longer  than  in  the 
frog  after  destroying  the  medulla.  Capillary  circulation 
will  go  on  in  the  lungs  of  the  frog  after  tying  the  trachea, 
as  I  stated  when  describing  the  circulation  as  seen  in  vari- 
ous parts  of  the  animal,  the  blood  being  suf^ciently  aerated 
by  means  of  the  skin. 

Thus  it  is  experimentally  proved  that  an  oxygenated 
state  of  the  blood  is  an  indispensable  condition  for  its  circu- 
lation through  the  capillaries.  When  the  process  of  respi- 
ration, or  aeration  of  the  blood,  is  interrupted,  the  blood 
cannot  circulate.  This  is  an  acknowledged  fact;  but  I  have 
shown,  by  the  preceding  experiments,  that  in  asphyxia  the 
impediment  to  the  circulation  is  in  the  capillaries;  that 
the  condition  of  oxygenation  is  necessary  to  the  per- 
formance of  the  vital  functions;  and  it  may  be  that  the  en- 
tire want  of  the  "  capillary  power  "  throws  all  the  onus  on 
the  heart,  and  that  the  heart  is  insufficient  for  the  labor. 
In  one  of  my  experiments,  after  the  capillary  circulation  had 
entirely  ceased,  the  chest  was  opened  and  the  heart  was 
found  beating  regularly. 


Ill 

EXPERIMENTS  ON  THE  RECURRENT  SENSI- 
BILITY OF  THE  ANTERIOR  ROOTS  OF  THE 
SPINAL  NERVES 

Published  in  the  "  New  Orleans  Medical  Times,"  in  1861. 

There  are  few  facts  in  physiology  better  known  and 
more  generally  admitted  than  those  which  have  refer- 
ence to  the  properties  of  the  two  roots  of  the  spinal 
nerves.  The  anterior  roots  are  motor  and  the  posterior 
roots  are  sensory.  Like  most  important  discoveries, 
however,  the  credit  of  its  authorship  has  been  somewhat 
disputed,  though  it  is  now  usually  conceded  to  Sir  Charles 
Bell.  It  is  a  curious  fact,  nevertheless,  that  in  1809,  two 
years  before  the  appearance  of  Sir  Charles  Bell's  first 
essay,  Mr.  Alexander  Walker,  an  English  physician,  ad- 
vanced the  idea  that  the  two  roots  of  origin  of  the  spinal 
nerves  had  dififerent  properties;  but  he  supposed  that  the 
posterior  roots  were  motor  and  the  anterior  roots  sen- 
sory. To  support  this  view,  which  was  a  mere  supposi- 
tion, Walker  brought  neither  physiological  nor  patho- 
logical proofs;  but  in  181 1,  Charles  Bell  made  the  great 
discovery  with  which  his  name  is  connected;  viz.,  that 
the  posterior  roots  conducted  sensations  and  that  their 
irritation  produced  no  movements,  while  the  anterior 
roots  were  motor,  as  proved  by  the  occurrence  of  mus- 
cular movements  when  they  were  stimulated.  Bell,  how- 
ever, was  not  a  vivisector;  his  experiments  were  chiefly 
on  rabbits,  which  he  killed  suddenly,  opened  the  spinal 
canal  and  irritated  the  posterior  and  anterior  roots  of 
the  nerves,  the  experiments  resulting,  as  just  stated,  in 
movements  of  muscles  when  the  anterior  roots  were 
stimulated,  and  none  when  the  same  stimulation  was  ap- 
plied  to   the   posterior   roots.      These   experiments   were 

repeated   by   French   and   German   physiologists,   among 

29 


30  RECURRENT   SENSIBILITY 

whom  were  Miiller,  Valentin,  Magendie  and  Longet. 
Longet,  especially,  carried  Bell's  experiments  on  the 
nerve-roots  to  the  columns  of  the  cord  and  demonstrated 
that  the  anterior  columns  were  motor  while  the  poste- 
rior were  sensory.  He  also  made  a  number  of  confirma- 
tory experiments  upon  the  roots  of  the  nerves  in  living 
animals. 

The  experiments  which  are  chiefly  to  be  noticed  in 
the  present  communication  were  made  by  Magendie; 
who,  though  many  physiological  facts  had  of  course  al- 
ready been  arrived  at  by  experiment,  may  be  said  to  be 
the  father  of  the  experimental  school  of  physiology.  He 
made  experiments,  which  were  published  in  1822,  upon 
the  roots  of  the  spinal  nerves,  and  found  that  while  the 
posterior  roots  were  purely  sensory,  the  anterior  roots, 
were  not,  in  all  of  his  observations,  purely  motor,  but  some- 
times possessed  a  slight  degree  of  sensibility.  These  ex- 
periments he  repeated  in  1839  and  was  able  to  establish  at 
that  time  a  certain  degree  of  sensibility  in  the  anterior  roots. 
He  also  showed  that  the  facial  possessed  some  sensibility 
and  that  this  was  derived  from  the  fifth  pair.  This  he  called 
the  "  recurrent  sensibility;  "  and  these  experiments  tended 
to  show  that  the  views  of  Sir  Charles  Bell  and  his  followers 
had  been  too  exclusive;  that  the  anterior,  or  motor  roots 
possessed  a  certain  degree  of  sensibility,  though  not  so 
acute  as  in  the  posterior  roots.  Here  is  met  a  curious  event 
in  the  history  of  the  recurrent  sensibility:  Magendie's  ex- 
periments, being  in  a  manner  opposed  to  the  views  of  Bell, 
which  were  then  universally  received,  attracted  consider- 
able notice;  but  when,  after  1839,  he  attempted  to  repeat 
them,  he  utterly  failed,  and  finally  abandoned  the  ground 
that  he  had  taken — one  of  the  many  examples  of  the  hon- 
esty of  description  which  mark  the  experiments  of  this  dis- 
tinguished physiologist.  It  was  not  until  1846  that  Ber- 
nard revived  "  recurrent  sensibility "  and  succeeded  in 
again  demonstrating  it.  He  remembered  that  in  1839  the 
experiments  for  the  lectures  of  Magendie  were  prepared  in 
the  morning,  and  that  the  animals  used  for  the  purpose  of 
demonstrating  recurrent  sensibility  were  thus  permitted  a 
period  of  repose  before  demonstrations  were  made  during 
the  lecture,  which  took  place  in  the  afternoon.  He  himself 
had  made  operations  on  the  spinal  cord  and  roots  of  the 


RECURRENT    SENSIBILITY  31 

nerves,  and  had  found  that  after  the  operation  of  opening 
the  spinal  canal,  which  is  exceedingly  painful  and  tedious, 
the  general  sensibility  of  the  animal  was  blunted.  The 
state  of  the  nerves,  then,  was  more  natural  after  the  animal 
had  been  permitted  to  recover  from  the  first  effects  of  the 
operation  than  immediately  after  the  exposure  of  the  roots. 
Carrying  this  idea  into  practice,  he  opened  the  spinal  canal 
in  dogs  and  allowed  them  two  or  three  hours'  repose  before 
he  made  his  observations  on  the  roots  of  the  nerves.  In 
experiments  conducted  in  this  way,  especially  in  dogs  that 
were  vigorous  and  well  nourished,  he  always  found  the  an- 
terior roots  of  the  nerves  sensitive.  He  found,  also,  that 
the  sensibility  was  derived  from  the  posterior  roots;  for  the 
division  of  these  immediately  abolished  the  sensibility  of 
the  anterior  roots.  He  made  in  addition  some  interesting 
observations  upon  the  disappearance  of  sensibility  from  ex- 
haustion, anesthetics  and  other  causes.  He  showed  that 
sensibility  first  disappeared  in  the  anterior  roots,  then  in 
the  periphery  and  last  in  the  posterior  roots.  When  the 
sensibility  reappeared,  it  was  first  manifest  in  the  posterior 
roots,  then  in  the  periphery  and  last  in  the  anterior  roots. 
These  experiments  of  Bernard  have  fully  established  the 
fact  of  recurrent  sensibility;  but  so  far  as  I  am  aware,  they 
have  been  repeated  and  confirmed  only  by  Schiff. 

As  I  have  lately  had  occasion  to  repeat  these  experi- 
ments at  the  New  Orleans  School  of  Medicine  and  to 
demonstrate  to  the  class,  in  my  regular  course  of  lectures, 
recurrent  sensibility,  I  have  thought  the  subject  sufficient- 
ly interesting  to  put  upon  record  my  own  experiments 
which  confirm  the  view  held  by  Magendie,  in  1839, 
afterward  abandoned  by  him  but  confirmed  in  1846  by 
Bernard. 

Bernard's  experiments  were  made  before  the  use  of 
ether  as  an  anesthetic;  but  Schiff,  who  repeated  these  ex- 
periments at  a  later  date,  always  made  use  of  ether  in  the 
operation  of  opening  the  spinal  canal.  This  of  course 
abolishes  pain  during  the  preliminary  operation;  and  in  the 
course  of  one  or  two  hours  the  animal  entirely  recovers 
from  its  effects  and  is  ready  for  the  observations  on  the 
nerve-roots.  It  is  best  to  select  a  vigorous  healthy  dog 
for  the  operation  as  the  sensibility  is  then  much  more 
marked.    The  most  convenient  situation,  also,  at  which  to 


32  RECURRENT    SENSIBILITY 

ojicn  the  spinal  canal  is  in  the  Inmbar  rci^ion  at  the  point 
of  junction  of  the  iliac  bones  with  the  spinal  column. 

Experiment  I. — February  15,  1861,  11  a.m.  A  vigorous  me- 
dium-sized dog  was  completely  etherized,  placed  on  his  belly  on  the 
table,  with  a  billet  of  wood  under  the  lumbar  region  to  make  this 
part  of  the  spinal  column  prominent.  The  hair  was  then  cut  from 
the  i)arts  to  be  incised,  and  a  longitudinal  incision  about  four  inches 
in  length  was  made  just  to  the  left  of  the  spinous  processes  of  the 
lower  lumbar  vertebrae.  This  incision  was  then  carried  down  by 
the  sides  of  the  spinous  processes  to  their  junction  witb  the  laminae. 
The  lamin.-e  of  the  fifth,  sixth  and  seventh  lumbar  vertebra;  were 
then  denuded  of  their  muscles  and  were  cut  through  vertically  by 
a  fine  saw  carried  as  near  the  spinous  processes  as  possible.  The 
laminre  were  then  divided  near  the  transverse  processes,  by  a  cut 
of  the  saw  parallel  to  the  first  but  directed  obliquely  inward.  There 
is  danger  in  making  this  second  cut  of  wounding  the  nerves  as  they 
emerge  from  the  spinal  canal  and  also  of  opening  the  vertebral 
sinus;  but  this  may  be  avoided  by  cutting  wath  great  care,  not  going 
through  the  lamin?e  entirely  but  breaking  them  off  by  prying  with 
a  chisel  introduced  into  the  cut  next  the  spinous  processes.  In 
opening  the  spinal  canal  the  roots  of  the  fifth  pair  of  lumbar  nerves 
were  divided.  The  roots  of  the  ixth  pair,  however,  were  intact. 
These  roots  were  separated  carefully  by  a  delicate  blunt  hook, 
threads  were  passed  beneath  them,  the  wound  was  closed  by  su- 
tures and  the  animal  set  at  liberty.  After  recovering  from  the 
effects  of  the  ether,  it  was  discovered  that  his  left  posterior  ex- 
tremity was  partially,  though  not  completely  paralyzed,  owing  to 
the  injury  to  the  nerves  during  the  operation  of  opening  the  spinal 
canal. 

February  16,  11  a.m.  Twenty- four  hours  after  the  operation 
the  wound  was  opened;  the  discharges,  which  had  been  consider- 
able, were  removed,  and  irritation  by  means  of  pinching  with  for- 
ceps was  applied  to  the  roots  of  the  nerves.  Both  roots  were  sen- 
sitive, as  manifested  by  the  cries  of  the  animal,  but  the  sensibility 
of  the  posterior  root  was  by  far  the  more  acute. 

The  wound  was  then  again  closed  and  the  same  experiments 
were  made  before  the  medical  class,  at  2  p.  m.  The  sensibility 
of  the  posterior  root  was  then  acute;  but  the  sensibility  of  the  an- 
terior root  had  considerably  diminished,  probably  on  account  of 
exhaustion  produced  by  the  experiment  at  11  a.  m. 

Experiment  II. — February  16,  11.30  a.m.  The  dog  used  in 
this  experiment  was  a  larger,  younger  and  more  vigorous  dog 
than  the  one  used  in  Experiment  I.  The  animal  was  etherized  and 
the  incisions  made,  denuding  the  spinous  processes  and  laminae  of 
the  sixth  and  seventh  lumbar  vertebrae,  as  in  Experiment  I,  with 
the  difference  that  the  operation  was  made  on  the  right  side.  The 
laminae  of  the  sixth  and  seventh  lumbar  vertebrae  were  then  re- 
moved W'ithout  wounding  the  roots  of  any  of  the  nerves.  This  was 
done  by  makmg  the  cut  witb  the  saw  farthest  from  the  spinous 
processes  extend  only  partially  through  the  bone  and  then  removing 


RECURRENT    SENSIBILITY  33 

the  laminae  by  prying  them  off  with  a  chisel.  The  roots  of  the 
sixth  lumbar  nerves  were  then  isolated,  and  threads  of  fine  silk 
were  passed  beneath  them.  The  wound  was  then  closed  and  the 
animal  set  at  liberty.  The  operation  lasted  about  three  quarters 
of  an  hour. 

2  p.  M.  The  animal  was  exhibited  to  the  medical  class  and 
the  following  observations  were  made.  The  slightest  touch  of  the 
posterior  root  produced  intense  pain  manifested  by  cries.  Upon 
pinching  the  anterior  root,  the  animal  cried,  evidently  suffer- 
ing pain  though  not  so  intensely  as  when  the  posterior  root  was 
barely  touched.  Care  was  taken  in  irritating  the  anterior  root  not 
to  touch  the  posterior  root.  The  posterior  root  was  then  divided, 
its  section  causing  intense  pain,  and  the  anterior  root  was  again 
irritated.  Now,  however,  its  sensibility  had  entirely  disappeared, 
and  it  could  be  contused  in  the  roughest  manner  without  producing 
any  evidence  of  suffering. 

The  operation  for  the  purpose  of  exposing  the  spinal 
cord  is  quite  difficult  and  tedious,  on  account  of  hemor- 
rhage, which  is  sometimes  abundant,  and  difficulty  in  avoid- 
ing injury  of  the  roots  of  the  nerves  and  opening  the  ver- 
tebral sinus.  These  accidents  can  be  avoided,  however, 
with  a  little  practice.  The  instruments  necessary  for  open- 
ing the  spinal  canal  are  a  small  saw,  a  Hey's  saw,  a  pair  of 
small  bone-nippers  and  a  chisel.  When  the  laminae  of  the 
vertebrae  have  been  removed,  the  spinal  cord  is  exposed, 
surrounded  by  a  certain  quantity  of  fat  which  should  be 
carefully  removed  with  forceps.  A  pair  of  small  blunt 
hooks  are  then  necessary  for  the  purpose  of  isolating  and 
catching  up  the  roots  of  the  nerves.  It  is  best  then  to 
pass  a  fine  thread  under  the  nerves  before  closing  the 
wound,  so  as  to  be  able  easily  to  find  them  again.  The 
wound  is  then  to  be  closed  and  the  animal  allowed  to 
repose  for  two  or  three  hours,  when  it  will  have  re- 
covered entirely  from  the  effects  of  the  operation  and  the 
roots  of  the  nerves  will  have  regained  their  normal  sen- 
sibility. 

I  have  thus  detailed  two  experiments  which  show  in  a 
marked  manner,  especially  Experiment  II,  that  the  anterior 
roots  of  the  spinal  nerves  are  not  exclusively  motor  but 
that  they  possess  a  certain  degree  of  sensibility;  that  this 
sensibility  is  recurrent  and  is  derived  from  the  posterior,  or 
sensory  roots;  and  that  after  the  division  of  these  roots,  it 
is  immediately  lost.  In  this  I  have  confirmed  the  experi- 
ments of  Magendie,  in  1822  and  1839,  experiments  which 
3 


34  RECURRENT    SENSIBILITY 

he  failed  to  repeat  with  success  after  that  date,  which  were 
repeated  in  1846  by  Bernard,  and  later  still  by  Schiff,  but 
have  never  been  repeated,  so  far  as  I  am  aware,  ni  England 
or  this  country.  In  these  experiments  I  have  attempted 
to  show  nothing  beyond  the  recurrent  sensibility  and  its 
derivation  from  the  posterior,  or  sensory  roots. 


IV 

HISTORICAL  CONSIDERATIONS  CONCERNING 
THE  PROPERTIES  OF  THE  ROOTS  OF  THE 
SPINAL    NERVES 

Published  in  the  "  Quarterly  Journal  of  Psychological  Medicine  "  for  October, 

1868. 

At  the  time  when  the  functions  of  the  nerves  given  off 
from  the  spinal  cord  began  to  be  understood  by  physiolo- 
gists, there  was  much  discussion  in  regard  to  the  claims 
of  different  observers  to  the  honor  of  the  discovery  of  the 
different  properties  of  their  anterior  and  posterior  roots. 
Alexander  Walker,*  Sir  Charles  Bell  f  and  Herbert  jNIayo.:}: 
in  England,  all  claimed  a  share,  more  or  less  considerable, 
in  this  great  discovery:  and  in  France.  Magendie  *  pro- 
fessed to  have  been  the  first  to  demonstrate  this  important 
fact  by  direct  experiment. 

*  Walker,  "  The  Nervous  System,  anatomical  and  physiological  :  in  which 
the  functions  of  the  various  parts  of  the  brain  are  for  the  first  time  assigned, 
and  to  which  is  prefixed  some  account  of  the  author's  earliest  discoveries,  of 
which  the  more  recent  doctrine  of  Bell,  Magendie,  etc.,  is  shown  to  be  at 
once  a  plagiarism,  an  inversion,  and  a  blunder,  associated  with  useless  experi- 
ments, which  they  have  neither  understood  nor  explained."  London,  1S44, 
p.  50,  et  seq. 

f  Bell,  "  The  Nervous  System  of  the  Human  Body  :  as  explained  in  a 
series  of  papers  read  before  the  Royal  Society  of  London."  London,  1844, 
p.  13,  et  seq. 

Shaw,  "  Narrative  of  the  Discoveries  of  Sir  Charles  Bell  in  the  Nervous 
System."     London,  1839. 

X  Mayo,  "  Outlines  of  Human  Physiolog}'."     London,  1827,  p.  240. 

*  Magendie,  "  Experiences  sur  les  fonctions  des  racines  des  nerfs  rachi- 
diens," — Journal  de  physiologie.  Paris,  1822,  tome  ii.,  p.  276  ;  et  "  Expe- 
riences sur  les  fonctions  des  racines  des  nerfs  qui  naissent  de  la  moelle  epinere." 
Ibid.,  p.  366. 

Magendie  et  Desmoulins,  "  Anatomic  des  syst^mes  nerveux  des  animaux 
a  vertebres."     Paris,  1825,  tome  ii.,  p.  777. 

Magendie,  "  Precis  elementaire  de  physiologie."  Deuxieme  edition. 
Paris,  1825,  tome  i.,  pp.  167  and  216. 

"  Note    additionelle   aux    deuxieme   memoire    sur  les   nerfs  de   la 

face," — Journal  de  physiologie.     Paris,  1830,  tome  x.,  p.  189. 

"  Le9ons  sur  les   fonctions  et  les  maladies   du   systeme  nerveux." 

Paris,  1 841,  tome  i.,  p.  64. 

35 


36  ROOTS    OF   THE    SPINAL   NERVES 

The  pretensions  of  Walker  and  of  Mayo  are  easily  dis- 
posed of.  Walker,  who  was  undoubtedly  the  first  to  dis- 
tinctly state,  in  1809,  that  one  of  the  roots  of  the  nerves  was 
for  sensation,  while  the  other  presided  over  movements, 
did  not  support  his  theory  by  any  facts  or  experiments  and 
was  led  into  the  error  of  supposing  that  the  anterior  roots 
were  sensitive  and  the  posterior  were  motor,  precisely  the 
reverse  of  what  was  proved  to  be  the  case  by  the  subsequent 
experiments  of  Magendie.  Walker,  in  his  work,  ridicules 
the  idea  of  studying  the  functions  of  the  body  by  experi- 
ments on  living  animals;  yet  he  details  an  experiment,  "  the 
only  operation  on  a  living  animal  which  he  ever  has  per- 
formed, or  ever  will  perform,"  in  which  he  exposed  the 
roots  of  the  spinal  nerves  in  a  frog  and  found  "  that  irri- 
tation of  the  anterior  roots  caused  motion,  and  irritation 
of  the  posterior  caused  little  or  none."  *  Inasmuch  as 
Walker  claimed  in  his  publications,  as  late  as  1844,  that  he 
had  always  considered  the  posterior  roots  as  motor  and  the 
anterior  as  sensitive,  it  does  not  seem  that  he  has  any  well- 
founded  title  to  the  discovery  of  the  real  pro])erties  of  these 
nerves.  The  claims  of  Mayo  are  even  more  indefinite.  He 
simply  states,  long  after  the  publication  of  the  experiments 
of  Magendie,  that  "  the  remarkable  analogy  which  exists 
between  the  fifth  nerve  and  the  spinal  nerves,  led  me  to 
suppose  that  the  two  roots  of  the  spinal  nerves  had  the 
same  discrepancy  of  function  with  the  two  roots  of  the 
fifth;  and  that  the  ganglionic  portion  might  belong  to  sen- 
sation, the  smaller  anterior  portion  to  volition."  f 

All  discussion,  therefore,  relative  to  priority  in  the  dis- 
covery of  the  true  functions  of  the  roots  of  the  nerves  is 
confined  to  the  claims  of  Bell  and  of  Magendie.  The  ex- 
periments of  Midler  :|:  and  others  were  all  made  after  1822, 
the  date  of  the  first  publication  of  the  experiments  of  Ma- 
gendie in  the  "  Journal  de  physiologic." 

In  nearly  every  treatise  on  physiology  published  since 
1822  and  in  almost  all  w^orks  on  the  nervous  system  subse- 
quent to  that  date,  the  great  discovery  of  the  distinct  seat 
of  motion  and  sensation  in  the  spinal  nerves  is  ascribed  to 

*  Walker,  Oj>.  a'(.,  p.  i8.  \  Mayo,  Loc.  cit. 

%  Mliller,  "  Physiologic  du  systeme  nerveux."  Paris,  1840,  tome  i.,  p. 
85,  et  seq.  ;  and  "  Manuel  de  physiologie,"  Paris,  1851,  tome  i.,  p.  598,  et  seq. 
The  experiments  of  Miiller  were  first  published  in  1831. 


ROOTS    OF    THE    SPINAL    NERVES  37 

Sir  Charles  Bell.  The  name  of  Magendie  is  seldom  men- 
tioned in  this  connection,  even  in  France;  and  his  discov- 
eries are  supposed  to  relate  chiefly  to  the  seat  of  sensation 
and  motion  in  the  different  columns  of  the  spinal  cord. 

Before  discussing  the  real  claims  of  Bell  and  Magendie, 
it  may  not  be  uninteresting  to  review  the  statements  in 
some  of  the  more  common  works  by  English,  German 
and  French  authors.  Todd  and  Bowman  *  say  that  "  it 
can  not  be  denied  that  the  endowment  of  the  roots  was  dis- 
covered by  Bell;  "  Carpenter  f  says  "  that  the  merit  of  this 
discovery  is  almost  entirely  due  to  Sir  Charles  Bell;" 
Kirkes  :{:  makes  the  same  statement;  Bostock  *  associates 
the  names  of  Bell  and  Magendie  but  says  that  the  experi- 
ments of  Bell  were  clearly  antecedent  to  those  of  Magen- 
die; but  Elliotson.il  who  had  evidently  consulted  carefully 
the  literature  of  the  subject,  distinctly  asserts  that  Bell  had 
no  idea  that  the  anterior  roots  of  the  spinal  nerves  were 
motor  and  the  posterior  roots  sensory,  before  the  publica- 
tion of  Magendie's  experiments  in  1822;  and  he  ascribes 
the  whole  honor  of  the  discovery  to  Magendie.  So  far  as 
I  am  aware,  Elliotson  is  the  only  English  writer,  except 
Walker  and  Mayo,  who  themselves  laid  claim  to  the  dis- 
covery, who  does  not  ascribe  the  whole  honor  to  Bell.^ 

In  all  the  German  works  which  I  have  examined,  the 
credit  of  the  discovery  is  given  to  Bell.  Reference  has 
already  been  made  to  the  work  of  Miiller  on  the  nervous 
system, 0  and  his  manual  of  physiology. 1^  The  discovery  is 
also  unreservedly  ascribed  to  Bell  by  Valentin,^  by  Volk- 
mann  I  and  by  Budge.** 

*  Todd  and  Bowman,  "  The  Physiological  Anatomy  and  Physiology  of 
Man."     Philadelphia,  1857,  p.  274. 

f  Carpenter,  "  Principles  of  Human  Physiology."    Philadelphia,  1853,  p.  651. 
i  Kirkes,  "  Manual  of  Physiology."     Philadelphia,  1857,  p.  327. 

*  Bostock,  "An  Elementary  System  of  Physiology."  London,  1824,  vol. 
i.,  p.  281. 

II  Elliotson,  "  Human  Physiology."     London,  1840,  p.  465. 

^  I  should  also  except  the  author  of  a  review  in  the  "  London  Medical 
and  Physical  Journal  "  for  1829.     This  review  will  be  referred  to  hereafter. 

^  Op.  a'L,  p.  85. 

t  Op.  cit.,  p.  598. 

%  Valentin,  "  Lehrbuch  der  Physiologie  des  Menschen."  Braunschweig, 
1844,  Band  ii.,  S.  627. 

I  Volkmann,  in  "  Wagner's  Handworterbuch  der  Physiologie."  Braun- 
schweig, 1S44,  Band  ii.,  S.  558. 

**  Budge,  "  Lehrbuch  der  Speciellen  Physiologie  des  Menschen."  Leipzig, 
1862,  S.  623. 


38  ROOTS    OF    THE    SPINAL    NERVES 

The  most  interesting  bibliographical  researches  on  this 
subject  are  in  connection  with  the  French  treatises  on  phys- 
iology and  on  the  nervous  system.  In  1816  Magendie 
published  his  "  Precis  elementaire  de  physiologic,"  which, 
in  its  arrangement  and  the  general  method  of  considering 
the  subject,  has  served  as  the  model  of  the  best  works  on 
physiology  which  have  appeared  since  that  date.  In  his 
various  publications  already  referred  to,  and  in  the  second 
edition  of  the  "  Precis  elementaire,"  published  in  1825,  as 
well  as  in  subsequent  editions  of  the  same  work,  Magendie 
formally  lays  claim  to  the  credit  of  the  discovery  of  the 
functions  of  the  roots  of  the  nerves;  and  in  the  "  Journal  de 
physiologic  "  *  he  gives  full  credit  to  Sir  Charles  Bell  for 
his  observations,  quoting,  in  the  original,  the  account  of 
the  only  experiment  performed  by  Bell;  and  yet,  with  one 
or  two  exceptions,  all  the  French  works  which  treat  of  the 
subject  seem  to  regard  Sir  Charles  Bell  as  the  real  discover- 
er. The  author  to  whom  I  particularly  refer  as  the  excep- 
tion is  Vulpian,  who  has  lately  published  a  very  interesting 
work  on  the  nervous  system.  Vulpian  does  not  distinctly 
state  that  he  has  consulted  the  original  memoir  printed  by 
Bell  in  181 1,  but  he  seems  to  appreciate  so  fully  the  state 
of  the  question  that  the  present  review  would  have  been 
rendered  unnecessary  had  I  not  been  enabled  to  produce 
an  exact  reprint  of  the  original  memoir  f  (of  the  existence 
of  which  Vulpian  does  not  seem  to  be  aware),  and  from  this 
to  confirm  fully  the  statements  in  regard  to  the  priority 
in  this  great  discovery.  Vulpian  :|:  recognizes  fully  the  in- 
justice which  Magendie  has  so  long  received,  and  exposes, 
also,  the  unwarrantable  alterations  wdiich  Bell  has  made  in 
a  paper  originally  published  in  the  "  Philosophical  Trans- 
actions "  in  1 82 1,  and  reprinted  subsequently  in  1844.*  In 
the  reprint  of  this  paper  Bell  has  not  hesitated  to  so  modify 
his  language  as  to  make  his  remarks  correspond  with  the 
facts  discovered  by  Magendie  in  1822,  giving  to  the  reader 
the  impression  that  he  held  these  opinions  as  early  as  1821. 

*  Tome  X.,  p.  370. 

•f  "  Documents  and  Dates  of  Modern  Discoveries  in  the  Nervous  System." 
London,  John  Churchill,  1839,  p.  37,  et  seq. 

\  Vulpian,  "  Le9ons  sur  la  physiologic  generale  et  comparee  du  systeme 
nerveux."     Paris,  1866,  pp.  109  et  127. 

*  Bell,  "  The  Nervous  System  of  the  Human  Body  :  as  explained  in  a  series 
of  papers  read  before  the  Royal  Society  of  London."     London,  1844,  p.  33. 


ROOTS    OF   THE    SPINAL    NERVES  39 

Longet  in  his  work  on  the  nervous  system  says:  "  We 
see  that,  without  having  absohitely  demonstrated  it,  Ch. 
Bell  suspected  that  the  role  of  the  posterior  roots  relates 
to  sensibility."  *  In  this  work  Longet  quotes  from  Bell's 
memoir  of  181 1  reprinted  in  the  "  Documents  and  Dates 
of  Modern  Discoveries  in  the  Nervous  System."  The  same 
passage  occurs  in  Longet's  "  Traite  de  physiologic,"  but 
the  quotations  are  here  made  from  the  English  and  the 
French  editions  of  the  work  of  Mr.  Shaw.f  Among  the 
other  French  authors  who  ascribe  the  discovery  of  the  prop- 
erties of  the  roots  of  the  spinal  nerves  to  Ch.  Bell,  may  be 
mentioned  Beclard,:j:  Flourens,*  Foville  ||  and  Gratiolet.^ 
All  of  these  authors,  with  enthusiasm,  ascribe  to  Charles 
Bell  the  great  discovery  which  I  shall  show  belongs  to 
Magendie. 


REVIEW  OF  THE  CLAIMS  OF  SIR  CHARLES  BELL  TO  THE 
DISCOVERY  OF  THE  PROPERTIES  OF  THE  ROOTS  OF  THE 
SPINAL  NERVES,  AS  SHOWN  BY  HIS  WRITINGS,  AND  BY 
THE    NARRATIVE    OF    HIS    DISCOVERIES,    BY   MR.    SHAW 

The  original  memoir  by  Sir  Charles  Bell,  entitled  "  Idea 
of  a  New  Anatomy  of  the  Brain,"  which  was  printed  in 
1811,0  is  now  almost  inaccessible.  It  was  printed  for 
private  distribution  and  it  is  said  that  the  number  of  copies 

*  Longet,  "  Anatomic  et  physiologic  du  systeme  nerveux  de  ''homme  at  des 
animaux  vertebres."     Paris,  1832,  tome  i.,  p.  28. 

f  Longet,  "  Traite  de  physiologic. "     Paris,  i860,  p.  172. 

:]:  Beclard,    "  Traite   elementaire    de   physiologic    humainc."      Paris,    1859, 

*  Flourens,  "  Rccherchcs  experimentales  sur  Ics  proprietes  et  Ics  fonc- 
tions  du  systeme  nerveux  dans  Ics  animaux  vertebres."  Paris,  1842,  p.  13. 
Flourens,  in  his  Memoir  of  Magendie  read  at  the  Academy  of  Sciences,  soon 
after  the  death  of  this  great  physiologist,  in  1S55,  again  ascribes  the  credit  of 
the  discovery  of  the  different  properties  of  the  roots  of  the  spinal  nerves  to 
Charles  Bell.  A  translation  of  this  memoir  is  published  in  the  Smithsonian 
Report  for  1866,  p.  gi,  et  seq. 

II  Foville,  "  Tr«ite  complct  de  I'anatomie,  de  la  physiologic  ct  de  la 
pathologic  du  systeme  nerveux  cerebro- spinal  (i^re  partie)  anatomic."  Paris, 
1S44,  p.  493. 

"^  Lcuret  et  Gratiolet,  "  Anatomic  comparec  du  systeme  nerveux  considere 
dans  ses  rapports  avec  rintelligencc."     Paris,  1839-1857,  tome  ii  ,  p.  330. 

^  In  a  paper  read  before  the  Medico-Chirurgical  Society,  in  April,  1822, 
Mr.  J.  Shaw  gives  the  date  of  the  first  paper  by  Charles  Bell  as  1809.  This 
error  is  quoted  into  many  reviews  and  other  publications,  but  it  has  been  cor- 
rected by  Bell  himself  and  by  Mr.  Shaw.  (Alexander  Shaw's  "  Narrative  of  the 
Discoveries  of  Sir  Charles  Bell  in  the  Nervous  System,"  London,  1830,  p.  14.) 


40  ROOTS   OF   THE   SPINAL   NERVES 

was  only  one  hundred.*  From  the  writings  of  various  au- 
thors who  have  discussed  the  claims  of  Bell  and  of  Magen- 
die,  it  appears  that  few  have  had  the  opportunity  of  con- 
sulting the  original  paper.  It  is,  of  course,  frequently  re- 
ferred to  by  Bell  himself,  and  by  Mr.  Shaw,  his  brother-in- 
law.  Magendie  speaks  of  having  obtained  a  copy  of  this 
work  and  gives  a  quotation  from  it  in  the  "  Journal  de 
physiologie,"  f  Miiller  refers  to  the  original  paper  but 
does  not  definitely  state  that  he  has  had  the  opportunity 
of  consulting'it.ij;  In  a  review  published  in  the  "  London 
Medical  and  Physical  Journal  "  in  1829,  it  is  distinctly 
stated  that  the  original  paper  was  consulted;**  and  in  a 
reply  to  this  review  by  a  pupil  of  Charles  Bell,  published 
in  the  same  Journal,  in  1830,  reference  is  again  made. to 
the  original  tract.  ||  A  later  writer  in  the  "  British  and 
Foreign  Medico-Chirurgical  Review  "  assumes  to  have 
compared  the  reprint,  already  referred  to,  with  the  orig- 
inal paper.'^  With  these  exceptions,  no  author,  so  far 
as  I  know,  has  consulted  the  original  document ;  and 
the  claims  of  Charles  Bell  to  the  discovery  are  based 
upon  quotations  from  the  pamphlet  of  181 1,  made  by 
himself  and  by  Mr.  Shaw,  which  have  been  copied  into 
nearly  all  works  treating  of  the  physiology  of  the  nervous 
system.  Writers  on  this  subject  have  thus  been  forced  to 
get  their  ideas  of  the  claims  of  Charles  Bell  from  his  later 
publications,  particularly  his  work  on  the  nervous  system,^ 
which  has  been  very .  widely  circulated  and  has  passed 
through  several  editions.  I  have  before  me  a  w^ork,  appar- 
ently very  little  known,  entitled  "  Documents  and  Dates 
of  Modern  Discoveries  in  the  Nervous  System,"  published 
in  London,  in  1839,  by  John  Churchill.  This  volume  con- 
tains a  reprint  of  the  original  paper  of  Charles  Bell,  entire. 
So  far  as  I  have  been  able  to  compare  this  reprint  with  the 

*  Vulpian,  "  Le9ons  sur  la  physiologie  generale  et  comparee  du  syst^me 
nerveux,"  Paris,  1866,  p.  109. 

f  Op.  cit.,  tome  ii.,  p.  370. 

\  Miiller,  "  Physiologie  du  systeme  nerveux,"  Paris,  1840,  tome  i.,  p.  85. 

*  "  The  London  Medical  and  Physical  Journal,"  1829,  vol.  Ixii.,  p.  525. 

II  Ibid.,  1830,  vol.  Ixiii.,  p.  40.  This  writer  refers  to  the  tract  as  printed 
in  i8og. 

•^  "  The  British  and  Foreign  Medico-Chirurgical  Review,"  London,  1840, 
vol.  ix.,  p.  98. 

0  Bell,  "  The  Nervous  System  of  the  Human  Body,"  third  edition,  London^ 
1844. 


ROOTS    OF   THE    SPINAL   NERVES  41 

quotations  from  the  original  by  Bell  and  by  Shaw,  it  has 
proved  to  be  entirely  accurate.  Its  accuracy  is  also  attested 
by  the  writer  in  the  "  Medico-Chirurgical  Review,"  already 
referred  to.  It  does  not  appear  that  this  volume  is  referred 
to  by  any  physiological  writers  except  Longet;*  and  it  is 
a  matter  of  surprise  that  this  distinguished  author,  if  he 
has  carefully  read  the  memoir  of  Charles  Bell,  can  refrain 
from  giving  to  Magendie  full  credit  for  his  brilliant  discov- 
ery. In  his  work  on  physiology, f  Longet  quotes  the  paper 
of  Bell  from  the  "  Narrative  "  of  Mr.  Shaw,  and  says  noth- 
ing about  the  '*  Documents  and  Dates."  It  is  all  the  more 
surprising  that  the  claims  of  Magendie  should  not  be  rec- 
ognized in  France,  when  an  English  writer,  Elliotson,  had 
already  rendered  him  full  justice,  which  was  also  given  him, 
in  1829,  by  a  reviewer  in  the  "  London  Medical  and  Phys- 
ical Journal,"  the  author  of  the  review  here  attributing 
"  this  great  discovery  entirely  to  Magendie."  X 

With  all  the  publications  by  Bell  and  Magendie  before 
us,  it  would  seem  that  now,  when  the  acrimony  of  contro- 
versy has  subsided,  we  should  be  able  to  settle  the  claims 
of  each  of  these  physiologists  to  the  discovery  under  consid- 
eration. I  shall  abstain  from  reviewing  the  discussions  of 
this  question  which  took  place  soon  after  the  publication 
of  Magendie's  experiments,  and  proceed  to  study  carefully 
the  various  publications  on  this  subject,  by  Bell  and  Ma- 
gendie, beginning  with  the  memoir  printed  in  181 1. 

VIEWS  OF  SIR  CHARLES  BELL,  IN  181I,  CONCERNING  THE 
PROPERTIES  OF  THE  ROOTS  OF  THE  SPINAL  NERVES, 
TAKEN  FROM  HIS  "  IDEA  OF  A  NEW  ANATOMY  OF  THE 
BRAIN  " 

Almost  all  the  quotations  which  I  shall  make  from  this 
remarkable  pamphlet  are  to  be  found  in  Shaw's  "  Narra- 
tive "  of  Bell's  discoveries,  a  work  which  is  sufTficiently 
common  and  accessible  and  which  certainly  presents  the 
claims  of  Bell  in  the  most  favorable  light  possible.     I  refer 

*  Longet,  "  Anatomic  et  physiologic  du  systeme  nerveux  de  rhomme  et 
des  animaux  vertebres,"  Paris,  1842,  tome  i.,  p.  27. 

This  reprint  of  Bell's  original  memoir  is  distinctly  referred  to  by  Bernard  in 
his  "  Rapport  sur  le  progr^s  et  la  marche  de  la  physiologic  generale  en  France," 
Paris,  1867,  p.  155,  which  has  appeared  since  this  review  was  written. 

+  Longet,  "  Traite  de  physiologic,"  Paris,  i860,  tome  ii.,  p.  172. 

I  Zoc.  cit.,  p.  532. 


42  ROOTS    OF    THE    SPINAL    NERVES 

the  reader  to  this  work  to  show  that  nothing  is  omitted  in 
the  following  quotations  which  has  an  important  bearing 
on  the  subject  under  consideration. 

After  a  short  notice  of  the  then  prevailing  opinions  con- 
cerning the  structure  and  functions  of  the  nerves  and  the 
encephalon,  Bell  proceeds  to  give  a  general  statement  of 
his  views,  as  follows: 

"  In  opposition  to  these  opinions,  I  have  to  offer  reasons  for  be- 
lieving that  the  cerebrum  and  cerebellum  are  different  in  function 
as  in  form ;  that  the  parts  of  the  cerebrum  have  different  functions ; 
and  that  the  nerves  which  we  trace  in  the  body  are  not  single  nerves 
possessing  various  powers,  but  bundles  of  different  nerves,  whose 
filaments  are  united  for  convenience  of  distribution,  but  which  are 
distinct  in  office,  as  they  are  in  origin,  from  the  brain. 

"  That  the  external  organs  of  the  senses  have  the  matter  of  the 
nerves  adapted  to  receive  certain  impressions,  while  the  correspond- 
ing organs  of  the  brain  are  put  in  activity  by  other  external  excite- 
ment. That  the  idea  or  perception  is  according  to  the  part  of  the 
brain  to  which  the  nerve  is  attached,  and  that  each  organ  has  a 
certain  limited  number  of  changes  to  be  wrought  upon  it  by  the 
external  impression. 

"  That  the  nerves  of  sense,  the  nerves  of  motion,  and  the  vital 
nerves,  are  distinct  through  their  whole  course,  though  they  seem 
sometimes  united  in  one  bundle;  and  that  they  depend  for  their 
attributes  on  the  organs  of  the  brain  to  which  they  are  severally 
attached. 

"  The  view  which  I  have  to  present  will  serve  to  show  why 
there  are  divisions,  and  many  distinct  parts  in  the  brain ;  why  some 
nerves  are  simple  in  their  origin  and  distribution,  and  others  intri- 
cate beyond  description.  It  will  explain  the  apparently  accidental 
connection  between  the  twigs  of  nerves.  It  will  do  away  with  the 
difficulty  of  conceiving  how  sensation  and  volition  should  be  the 
operation  of  the  same  nerve  at  the  same  moment.  It  will  show  how 
a  nerve  may  lose  one  property  and  retain  another;  and  it  will  give 
an  interest  to  the  labors  of  the  anatomist  in  tracing  the  nerves  " — 
(pp.  39,  40). 

This  extract  simply  shows  that  Bell  entertained  the 
opinion  prevalent  at  that  day,  that  all  the  nerves  derived 
their  properties  from  the  encephalon.  The  new  idea  which 
he  advances  is,  that  the  nerves  are  to  be  divided  into  nerves 
of  motioti,  nerves  of  sensation  and  vital  nerves,  which  last 
were  at  that  time  supposed  to  be  the  nerves  which  pre- 
sided over  the  organic  functions.  The  theoretical  division 
of  the  nervous  fibres  into  motor  and  sensory  had  been  made 
by  Alexander  Walker  in  1809;  '^  and  Willis  held  the  opin- 

*  Loc.  cit. 


ROOTS    OF    THE    SPINAL   NERVES  43 

ion  that  the  cerebellum,  from  which  Bell  supposed  that  the 
"  vital  nerves  "  were  derived,  presided  over  the  functions 
of  organic  life.  These  ideas,  therefore,  cannot  be  claimed 
as  original. 

After  some  general  considerations  concerning  the  struc- 
ture and  probable  function  of  different  parts  of  the  nervous 
system,  the  following  experiments  are  detailed: 

"  In  thinking  of  this  subject,  it  is  natural  to  expect  that  we 
should  be  able  to  put  the  matter  to  proof  by  experiment.  But  how 
is  this  to  be  accomplished,  since  any  experiment  direct  upon  the 
brain  itself  must  be  difficult,  if  not  impossible?  I  took  this  view 
of  the  subject.  The  medulla  spinalis  has  a  central  division,  and  also 
a  distinction  into  anterior  and  posterior  fasciculi,  corresponding 
with  the  anterior  and  posterior  portions  of  the  brain.  Further, 
we  can  trace  down  the  crura  of  the  cerebrum  into  the  anterior 
fasciculus  of  the  spinal  marrow,  and  the  crura  of  the  cerebellum 
into  the  posterior  fasciculus.  I  thought  that  here  I  might  have 
an  opportunity  of  touching  the  cerebellum,  as  it  were,  through  the 
posterior  portion  of  the  spinal  marrow,  and  the  cerebrum  by  the 
anterior  portion.  To  this  end  I  made  experiments,  which,  though 
they  were  not  conclusive,  encouraged  me  in  the  view  I  had  taken. 

"  I  found  that  injury  done  to  the  anterior  portion  of  the  spinal 
marrow  convulsed  the  animal  more  certainly  than  injury  done  to 
the  posterior  portion ;  but  I  found  it  difficult  to  make  the  experi- 
ment without  injuring  both  portions. 

"  Next,  considering  that  the  spinal  nerves  have  a  double  root, 
and  being  of  opinion  that  the  properties  of  the  nerves  are  derived 
from  their  connections  with  the  parts  of  the  brain,  I  thought  I  had 
an  opportunity  of  putting  my  opinion  to  the  test  of  experiment,  and 
of  proving  at  the  same  time  that  nerves  of  different  endowments 
were  in  the  same  cord,  and  held  together  by  the  same  sheath. 

"  On  laying  bare  the  roots  of  the  spinal  nerves,  I  found  that  I 
could  cut  across  the  posterior  fasciculus  of  nerves,  which  took  its 
origin  from  the  posterior  portion  of  the  spinal  marrow,  without 
convulsing  the  muscles  of  the  back;  but  that  on  touching  the  ante- 
rior fasciculus  with  the  point  of  the  knife,  the  muscles  of  the  back 
were  immediately  convulsed.  Such  were  my  reasons  for  conclud- 
ing that  the  cerebrum  and  the  cerebellum  were  parts  distinct  in 
function,  and  that  every  nerve  possessing  a  double  function  ob- 
tained that  by  having  a  double  root.  I  now  saw  the  meaning  of  the 
double  connection  of  the  nerves  with  the  spinal  marrow ;  and  also 
the  cause  of  that  seeming  intricacy  in  the  connections  of  the  nerves 
throughout  their  course,  which  were  not  double  in  their  origin. 

"  The  spinal  nerves  being  double,  and  having  their  roots  in  the 
spinal  marrow,  of  which  a  portion  comes  from  the  cerebrum  and  a 
portion  from  the  cerebellum,  they  convey  the  attributes  of  both 
grand  divisions  of  the  brain  to  every  part;  and  therefore  the  dis- 
tribution of  such  nerves  is  simple,  one  nerve  supplying  its  distinct 
part"— (pp.  50-52). 


44  ROOTS   OF   THE   SPINAL   NERVES 

The  above  quotation  embodies  all  the  experiments  de- 
tailed by  Bell  in  his  first  essay.  From  the  account  of  these 
experiments  given  by  Vulpian,  it  would  not  seem  that  he 
had  consulted  the  orignal  work.  Vuli)ian  speaks  of  the  first 
experiment  on  the  spinal  cord  as  performed  upon  a  rabbit 
recently  killed.  No  such  statement  is  made  in  the  original. 
He  also  speaks  of  the  experiment  upon  the  roots  of  the 
nerves  as  made  upon  a  living  animal.*  This  does  not 
appear  in  the  original.  On  the  contrary,  Bell  speaks 
of  cutting  across  the  posterior  roots  (p.  51)  without 
"convulsing  the  muscles  of  the  back,"  and  has  nothing 
to  say  about  the  sensibility,  which  certainly  would  have 
been  manifested  if  the  operation  had  been  performed  on 
a  living  animal. 

A  careful  review  of  the  last  quotation,  which  is  alsO' 
made  in  full  by  Shaw,  will  give  a  clear  idea  of  the  real  opin- 
ion of  Bell  concerning  the  different  properties  of  the  roots 
of  the  nerves.  He  evidently  regards  the  anterior  fasciculi 
of  the  cord  as  prolongations  of  the  crura  cerebri;  and  the 
posterior  fasciculi  as  prolongations  of  the  crura  cerebelli; 
and  he  found  that  injury  to  the  anterior  portion  of  the  cord 
produced  convulsions  "  more  certainly  "  than  injury  done 
to  the  posterior  portion.  He  next  assumes  that  the  double- 
roots  of  the  spinal  nerves  receive  their  properties  from  their 
connections  with  different  parts  of  the  brain  (the  cerebrum 
and  cerebellum);  and  his  experiments  on  the  roots  of  the 
nerves  agreeing  in  every  respect  with  the  experiments  upon 
the  anterior  and  posterior  fasciculi  of  the  cord,  he  concludes 
that  the  cerebrum  and  cerebellum,  and  consequently  the 
different  roots  of  the  spinal  nerves,  are  parts  distinct  in 
function. 

It  remains  now  to  see  what  distinct  functions  are  as- 
cribed to  the  cerebrum  and  cerebellum,  and  consequently 
to  the  nerves  proceeding  from  these  parts.  This  is  clearly 
indicated  in  the  following  quotation: 

"  The  cerebellum,  when  compared  with  the  cerebrum,  is  sim- 
ple in  its  form.  It  has  no  internal  tubercles  or  masses  of  cineritious 
matter  in  it.  The  medullary  matter  comes  down  from  the  cineritious 
cortex,  and  forms  the  crus ;  and  the  crus  runs  into  union  with  the 
same  process  from  the  cerebrum ;  and  they  together  form  the  me- 
dulla spinalis,  and  are  continued  down  into  the   spinal  marrow; 

*  Vulpian,  Op.  cit.,  p.  iii. 


ROOTS    OF   THE    SPINAL    NERVES  45 

and  these  crura  or  processes  afford  double  origin  to  the  double 
nerves  of  the  spine.  The  nerves  proceeding  from  the  crus  cere- 
belli  go  everywhere  (in  seeming  union  with  those  from  the  crus 
cerebri)  ;  they  unite  the  body  together,  and  control  the  actions  of 
the  bodily  frame ;  and  especially  govern  the  operation  of  the  vis- 
cera necessary  to  the  continuance  of  life.* 

"  In  all  animals  having  a  nervous  system,  the  cerebellum  is 
apparent,  even  though  there  be  no  cerebrum.  The  cerebrum  is  seen 
in  such  tribes  of  animals  as  have  organs  of  sense,  and  it  is  seen 
to  be  near  the  eyes,  a  principal  organ  of  sense;  and  sometimes  it 
is  quite  separate  from  the  cerebellum. 

"  The  cerebrum  I  consider  as  the  grand  organ  by  which  the 
mind  is  united  to  the  body.  Into  it  all  the  nerves  from  the  external 
•organs  of  the  senses  enter;  and  from  it  all  the  nerves  which  are 
agents  of  the  will  pass  out" — (pp.  53,  54). 

The  above  quotations  complete  the  history  of  Sir 
Charles  Bell's  ideas  in  regard  to  the  functions  of  the  roots 
of  the  nerves.  The  posterior  roots  are  supposed  to 
"  unite  the  body  together,  and  control  the  actions  of  the 
bodily  frame;  and  especially  govern  the  operation  of  the 
viscera  necessary  to  the  continuance  of  life."  The  anterior 
roots  convey  to  the  cerebrum  impressions  "  from  the  ex- 
ternal organs  of  the  senses,"  and  are  the  nerves  by  which 
the  agents  of  the  will  pass  out.  It  is  true  that  the  language 
is  not  very  clear  or  strictly  scientific  according  to  our 
present  ideas,  but  it  must  be  evident  to  every  one  that  Bell 
regarded  the  anterior  roots  as  nerves  of  both  motion  and 
sensation,  and  the  posterior  roots  as  the  so-called  "  vital  " 
nerves.  Indeed,  Mr.  Alexander  Shaw,  the  most  enthusi- 
astic and  persistent  partisan  of  Bell,  admits  the  uncertainty 
of  Bell's  statements  concerning  the  seat  of  sensation  in  the 
nervous  roots  in  the  following  passage:  "  Accordingly,  that 
it  is  left  in  doubt  by  Sir  Charles  Bell,  when  he  composed  his 
■*  Essay  on  the  Brain  '  in  181 1,  whether  the  power  of  giving 
sensation  belonged  to  the  posterior  root,  must  be  admit- 
ted." f  The  quotation  made  above,  which  was  omitted  by 
Mr.  Shaw,  shows  that  this  statement  is  not  strictly  correct. 
The  question  of  sensibility  of  the  posterior  roots  was  not 

*  This  important  paragraph,  in  which  the  functions  of  the  posterior  roots  of 
the  nerves  ("  the  nerves  proceeding  from  the  crus  cerebelli ")  are  distinctly 
assigned  without  a  mention  of  any  sensory  property,  is  not  quoted  by  Shaw  ; 
and  this  passage,  which  is  nowhere  contradicted,  makes  it  evident  that  Bell 
knew  nothing  and  discovered  nothing  of  the  properties  of  the  sensory  roots. 

f  Shaw,  "  Narrative  of  the  Discoveries  of  Sir  Charles  Bell  in  the  Nervous 
System."     London,  1839,  P-  4^- 


46  ROOTS    OF   THE    SPINAL    NERVES 

mentioned  by  Bell;  and,  far  from  being  "  left  in  doubt,"  an- 
other function  was  assigned. 

The  following  quotation  from  Bell's  work  reiterates  the 
supposed  functions  of  the  roots: 

"  The  convex  bodies,  which  are  seated  in  the  lower  part  of  the 
cerebrum,  and  into  which  the  nerves  of  sense  enter,  have  extensive 
connection  with  the  hemispheres  on  their  upper  part.  From  the 
nieduHary  matter  of  the  hemispheres,  again,  there  pass  down,  con- 
verging to  the  crura,  striae,  which  is  the  medullary  matter,  taking 
upon  it  the  character  of  a  nerve ;  for,  from  the  crura  cerebri,  or  its 
prolongation  in  the  anterior  fasciculi  of  the  spinal  marrow,  go  off 
the  nerves  of  motion. 

"  But  with  these  nerves  of  motion,  which  are  passing  outward, 
there  are  nerves  going  inward ;  nerves  from  the  surfaces  of  the 
body;  nerves  of  touch;  and  nerves  of  peculiar  sensibility,  having 
their  seat  in  the  body  or  viscera.  It  is  not  improbable  that  the 
tracts  of  cineritious  matter  which  we  observe  in  the  course  of  the 
medullary  matter  of  the  brain,  are  the  seat  of  such  peculiar  sensibili- 
ties;  the  organs  of  certain  powers  which  seem  resident  in  the  body  " 
—  (PP-  55.  56)- 

The  above  passage  leaves  no  doubt  that  Bell  thought 
that  the  nerves  of  motion,  going  off  from  the  anterior  fas- 
ciculi of  the  spinal  marrow,  contained  filaments  of  sensation 
in  the  same  sheath. 

The  last  paragraph  of  the  original  memoir,  which  ap- 
parently contains  the  conclusions  drawn  by  its  author  from 
his  facts  and  experiments,  should  never  have  been  omitted 
in  quotations  intended  to  give  a  correct  idea  of  the  views 
of  Sir  Charles  Bell,  as  exemplified  by  this  remarkable 
pamphlet.  This,  however,  is  not  quoted  by  Mr.  Shaw,  or,, 
so  far  as  I  can  ascertain,  by  any  other  writer.  This  para- 
graph needs  no  comment,  as  it  presents  the  views  of  the  au- 
thor more  clearly  than  any  other  passage: 

"  From  the  cineritious  matter,  which  is  chiefly  external,  and 
forming  the  surface  of  the  cerebrum ;  and  from  the  grand  centre 
of  the  medullary  matter  of  the  cerebrum,  what  are  called  the 
crura  descend.  These  are  fasciculated  processes  of  the  cerebrum, 
from  which  go  off  the  nerves  of  motion,  the  nerves  governing  the 
muscular  frame.  Through  the  nerves  of  sense  the  sensorium  re- 
ceives impressions,  but  the  will  is  expressed  through  the  medium 
of  the  nerves  of  motion.  The  secret  operations  of  the  bodily  frame, 
and  the  connections  which  unite  the  parts  of  the  body  into  a  sys- 
tem, are  through  the  cerebellum  and  the  nerves  proceeding  from 
it"— (p.  60). 

It  is  not  pretended  that  Charles  Bell  made  any  publica- 
tion concerning  the  functions  of  the  roots  of  the  spinal 


ROOTS    OF    THE    SPINAL    NERVES  47 

nerves  between  181 1  and  1821,  when  he  read  before  the 
"Royal  Society  of  London"  a  paper  "On  the  nerves; 
giving  an  account  of  some  experiments  on  their  structure 
and  functions,  which  lead  to  a  new  arrangement  of  the  sys- 
tem." In  this  article,  as  it  is  printed  in  the  "  Philosophical 
Transactions,"  182 1,  Part  I.,  p.  398,  ct  scq.,  there  is  no 
indication  that  the  author  was  aware  of  the  true  properties 
of  the  anterior  and  posterior  roots.  The  claims  of  Bell  to 
this  discovery,  then,  rest  entirely  on  the  unpublished 
pamphlet  of  181 1;  and  the  extracts  I  have  given  show  con- 
clusively that  he  attributed  to  the  posterior  roots  proper- 
ties w^hich  they  do  not  possess,  and  gave  to  the  anterior 
roots  the  properties  both  of  motion  and  sensation. 

The  state  of  the  question  in  181 1  may,  then,  be 
summed  up  in  a  very  few  words: 

In  1809,  Alexander  Walker  proposed  the  theory-  that 
one  of  the  roots  of  the  spinal  nerves  was  for  motion  and 
the  other  for  sensation.  This  was  done  on  purely  theoret- 
ical grounds;  and  Walker  erred  in  supposing  that  the  pos- 
terior roots  were  motor  and  the  anterior  sensory.* 

In  181 1,  Sir  Charles  Bell  advanced  the  views  which  I 
have  already  fully  given;  and  to  him  is  due  the  credit  of 
having  been  the  first  to  attempt  to  verify  his  theories  by 

*  Walker  states  his  theory  of  the  distinct  functions  of  the  roots  of  the  nerve 
in  the  following  words  : 

"  Thus,  then,  it  is  proven  to  us,  that  medullary  action  commences  in  the 
organs  of  sense  ;  passes,  in  a  general  manner,  to  the  spinal  marrow,  by  the  an- 
terior fascicula  of  the  spinal  nerv'es,  which  are,  therefore,  nerves  of  sensation, 
and  the  connections  of  which  with  the  spinal  marrow  or  brain  must  be  termed 
their  spinal  or  cerebral  terminations  ;  ascends  through  the  anterior  columns  of 
the  spinal  marrow,  which  are,  therefore,  its  ascending  columns  ;  passes  forward 
through  the  inferior  fasciculi  of  the  medulla  oblongata,  and  then  through  the 
crura  cerebri  ;  extends  forward,  outward,  and  upward  through  the  corpora 
striata  ;  and  reaches  the  hemispheres  of  the  cerebrum  itself.  This  precisely  is 
the  course  of  its  ascent  to  the  sensorium  commune. 

"  From  the  posterior  part  of  the  medulla  of  the  hemispheres,  it  returns  by 
the  thalami,  passing  backward,  inward,  and  downward  ;  flows  backward  in  the 
fasciculi  under  the  nates  and  testes  ;  backward  and  upward  through  the  pro- 
cesses cerebelli  ad  testes  or  anterior  peduncles  of  the  cerebellum  ;  and  thus 
reaches  the  medulla  of  the  cerebellum  itself. 

"  From  the  cerebellum  it  descends  through  the  posterior  columns  of  the 
spinal  marrow,  which  are,  therefore,  its  descending  columns  ;  and  expands 
through  the  posterior  fasciculi  of  all  the  nerves,  which  are,  therefore,  the  nerves 
of  volition,  and  the  connection  of  which  with  the  spinal  marrow  or  brain  must 
be  termed  their  spinal  or  cerebellic  origins.  This  precisely  is  the  course  of  its 
descent  from  the  sensorium  commune  toward  the  muscular  system." — ("  Docu- 
ments and  Dates  of  Modern  Discoveries  in  the  Nervous  System."  London, 
1839,  p.  36.) 


48  ROOTS    OF    THE    SPINAL    NERVES 

experiments.  He  was  iin(loiil:)te(lly  the  first  to  operate  upon 
the  roots  of  the  spinal  nerves  in  an  animal  recently  killed; 
but  he  was  far  from  attributing  to  each  root  its  proper  func- 
tion, which  was  done  by  Magendie   in  1822. 

REVIEW  OF  THE  WRITINGS  OF  SIR  CHARLES  BALL  SUBSE- 
QUENT TO  181  I,  IN  WHICH  IT  IS  IMPLIED  THAT  HE  DIS- 
COVERED THE  FUNCTIONS  OF  THE  ROOTS  OF  THE  SPINAL 
NERVES 

All  the  credit  which  I  have  to  give  to  Sir  Charles  Bell 
for  advances  in  the  anatomy  and  physiology  of  the  spinal 
nerves  must  cease  with  the  review  of  the  pamphlet  of  181 1. 
In  a  memoir  on  the  nerves  of  the  head,  read  before  the 
"  Royal  Society,"  July  12,  1821,  more  than  a  year  before 
the  publication  of  the  experiments  of  Magendie,  there  is 
no  mention  of  distinct  motor  and  sensory  roots  of  the 
spinal  nerves  or  of  distinct  properties  in  different  portions 
of  the  spinal  cord.  This  paper  was  republished  by  Bell, 
after  the  publication  of  Magendie's  observations,  in  a  work 
on  the  nervous  system;  and  it  is  this  republication  which  is 
most  accessible  and  most  frequently  referred  to  by  physio- 
logical writers.  The  republication  avowedly  contains 
"  some  additional  explanations;  "  but  a  careful  comparison 
of  it  with  the  original  shows  that  every  portion  of  it  that 
was  susceptible  of  such  verbal  alteration  has  been  modi- 
fied to  make  it  correspond  with  the  discovery,  by  Magen- 
die. But  at  the  same  time,  the  impression  received  by  the 
reader  is  that  it  is  essentially  the  same  as  the  memoir  pub- 
lished in  1 82 1.  These  alterations  have  been  commented 
upon  by  Vulpian;  but  I  propose  to  give  some  extracts  from 
the  two  papers,  side  by  side,  showing  how  the  unwarrant- 
able verbal  alterations  in  the  reprint  are  calculated  to  give 
the  impression  that  Bell  was  fully  aware  of  the  true  seat  of 
motion  and  sensation  in  the  spinal  cord  and  the  spinal 
nerves,  and  had  succeeded,  by  applying  the  same  mode  of 
investigation  to  the  nerves  of  the  brain,  in  demonstrating 
"  that  the  principle  in  question  held  good  equally  with  re- 
gard to  them  as  with  regard  to  the  spinal  nerves."  * 


*  "  This  is  claimed  for  Bell  by  his  brother-in-law,  Mr.  Alexander  Shaw,  from 
whom  the  above  passage  in  quotation  marks  is  taken." — (Shaw,  "  Narrative  of 
the  Discoveries  of  Charles  Bell  in  the  Nervous  System."     London,  1839,  p.  8.) 


ROOTS    OF   THE    SPINAL    NERVES 


49 


EXTRACTS  FROM  THE  MEMOIRS  OF  SIR  CHARLES  BELL,  PUB- 
LISHED IN  THE  PHILOSOPHICAL  TRANSACTIONS  AND  IN 
HIS    WORK    ON    THE    NERVOUS    SYSTEM  * 


On  the  nerves  ;  giving  an 
account  of  some  experiments 
on  their  strl'cture  and  func- 
tions, which  lead  to  a  new 
arrangement  of  the  system. 
By  Charles  Bell,  Esq.,  commu- 
nicated  by  Sir  Humphrev  Daw, 
Bart.,  P.  R.  S.  Read,  July  12, 
1821.  Philosophical  Transac- 
tions, London,  1821,  Part  L,  p. 
398,  et  seq. 


Original 

Of  THE  TRIGEMINUS,  OR  FIFTH 

PAIR.  In  all  animals  that  have 
a  stomach,  with  palpi  or  tentac- 
ula  to  embrace  their  food,  the 
rudiments  of  this  nerve  may  be 
perceived ;  and  always  in  the 
vermes,  that  part  of  their  nerv- 
ous system  is  most  easily  dis- 
cerned which  surrounds  the 
•oesophagus  near  the  mouth.  If 
a  feeler  of  any  kind  project 
from  the  head  of  an  animal, 
whether  the  antenna  of  a  lob- 
ster or  the  trunk  of  an  elephant, 
it  is  a  branch  of  this  nerve 
■which  supplies  sensibility  to  the 
member  and  animates  its  mus- 
cles. But  this  is  only  if  it  be 
a  simple  or^an  of  feeling,  and 
is  not  in  its  office  connected  with 
respiration. 


On    THE    nerves;    giving    a 

VIEW  OF  THEIR  STRUCTURE  AND 
ARRANGEMENT,  WITH  AN  AC- 
COUNT OF  SOME  EXPERIMENTS 
ILLUSTRATIVE  OF  THEIR  FUNC- 
TIONS. From  the  Philosophical 
Transactions,  1821,  with  some 
additional  explanations.  —  The 
nervous  system  of  the  human 
body,  as  explained  in  a  series  of 
papers  read  before  the  Royal 
Society  of  London.  By  Sir 
Charles  Bell,  K.  G.  H.,  etc.,  etc. 
Third  edition,  London,  1844,  p. 
33,  et  seq. 

Reprint 

Of  THE  TRIGEMINUS,  OR  FIFTH 

PAIR,  the  nerve  of  sensation  and 
mastication.  In  all  animals  that 
have  a  stomach,  with  palpi  or 
tentacula  to  embrace  their  food, 
the  rudiments  of  this  nerve  may 
be  perceived ;  and  always  in  the 
vermes,  that  part  of  their  nerv- 
ous system  is  most  easily  dis- 
cerned which  surrounds  the 
oesophagus  near  the  mouth.  If 
a  feeler  of  any  kind  project 
from  the  head  of  an  animal, 
whether  the  antenna  of  a  lob- 
ster or  the  trunk  of  an  elephant, 
it  is  by  a  branch  of  this  nerve 
that  it  is  supplied  with  sensibil- 
ity. But  if  it  be  not  merely  a 
simple  organ  of  feeling,  but  in 
its  office  connected  with  respira- 
tion, another  nerve  is  added. 
The  trunk  of  the  elephant  is  not 
a  simple  feeler;  it  is  a  tube 
through  zvhich  it  respires,  and 
therefore  it  has  a  different 
nerz'e  superadded,  to  move  it  as 
a  hand,  and  to  expand  it  in  the 
act  of  inspiration. 


*  The  passages  that  have  been  altered  are  printed  in  italics. 
4 


5° 


ROOTS    OF    THE    SPINAL    NERVES 


From  the  nerve  which  comes 
off  from  the  anterior  ganglion 
of  the  leech,  and  which  supplies 
its  mouth,  we  may  trace  up 
through  the  gradations  of  ani- 
mals a  nerve  of  taste  and  man- 
ducation,  until  we  arrive  at  the 
complete  distribution  of  the 
fifth,  or  trigeminus,  in  man. 
Here  in  the  highest  link,  as  in 
the  lowest,  the  nerve  is  subser- 
vient to  the  same  functions.  It 
is  the  nerve  of  taste  and  of  the 
salivary  glands;  of  the  muscles 
of  the  face  and  jaws,  and  of 
co)nnion  sensibility.  It  comes 
off  from  the  base  of  the  brain  in 
so  peculiar  a  situation,  that  it 
alone,  of  all  the  nerves  of  the 
head,  receives  roots  both  from 
the  medullary  process  of  the 
cerebrum  and  the  cerebellum. 
A  ganglion  is  formed  upon  it 
near  its  origin,  though  some  of 
its  filaments  pass  on  without  en- 
tering into  the  ganglion.  Be- 
fore passing  out  of  the  skull,  the 
nerve  splits  into  three  great 
divisions,  which  are  sent  to  the 
face,  jaws,  and  tongue.  Its 
branches  go  minutely  into  the 
skin,  and  enter  into  all  the  mus- 
cles, and  they  are  especially 
profuse  to  the  muscles  which 
move  the  lips  upon  the  teeth 
—  (pp.  409,  410). 


From  the  nerve  which  comes 
off  from  the  anterior  ganglion 
of  the  leech,  and  which  supplies 
its  mouth,  we  may  trace  up 
through  the  gradations  of  ani- 
mals a  nerve  of  taste  and  man- 
ducation,  until  we  arrive  at  the 
complete  distribution  of  the 
fifth,  or  trigeminus,  in  man. 
Here  in  the  highest  link,  as  in 
the  lowest,  the  nerve  is  subser- 
vient to  the  same  functions.  It 
is  the  nerve  of  the  muscles  of 
the  jaws,  and  of  common  sensi- 
bility, of  taste,  and  of  the  sali- 
vary glands.  It  comes  off  from 
the  base  of  the  brain  in  so  pecid- 
iar  a  situation,  that  it  alone,  of 
all  the  nerves  of  the  head,  re- 
ceives roots  both  from  the  col- 
umn of  sensibility  and  that  of 
motion.  A  ganglion  is  found 
upon  it  near  its  origin,  though 
some  of  its  filaments  pass  on 
without  entering  into  the  gan- 
glion. Before  passing  out  of 
the  skull,  the  nerve  splits  into 
three  great  divisions,  which  are 
sent  to  the  face,  jaws,  and 
tongue.  Its  branches  go  mi- 
nutely into  the  skin,  and  enter 
into  all  the  muscles,  and  they 
are  especially  profuse  to  the 
lips— (pp.  47,  48). 


Of  the  respiratory  nerve 
of  the  face,  being  that 
which  is  called  the  portio 
dura  of  the  seventh. 


Of   THE    PORTIO    DURA    OF    THE 

SEVENTH       NERVE THE       MOTOR 

AND       RESPIRATORY        NERVE       OF 
THE  FACE. 


In  this  extensive  distribution, 
the  nerve  penetrates  to  all  the 
muscles  of  the  face ;  muscles 
supplied  also  zvith  the  branches 
of  the  fifth  pair.  Its  branches 
penetrate  to  the  skin  accom- 
panying the  minute  vessels  of 
the  cheek — (p.  411). 


In  this  extensive  distribution, 
the  nerve  penetrates  to  all  the 
muscles  of  the  face ;  muscles 
supplied  also  with  the  sensitive 
branches  of  the  fifth  pair — 
(P-  50). 


ROOTS    OF    THE    SPINAL    NERVES 


51 


Experiments  on  the  nerves 
OF  THE  face. 

An  ass  being  thrown,  and  its 
nostrils  confined  for  a  few  sec- 
onds, so  as  to  make  it  pant  and 
forcibly  dilate  the  nostrils  at 
each  inspiration,  the  portio  dura 
was  divided  on  one  side  of  the 
,  head;  the  motion  of  the  nostril 
of  the  same  side  instantly  ceased, 
while  the  other  nostril  contin- 
ued to  expand  and  contract  in 
unison  with  the  motions  of  the 
chest. 


On  division  of  this  nerve,  the 
animal  will  give  no  sign  of 
pain ;  or  in  no  degree  equal  to 
what  results  from  dividing  the 
fifth   nerve. 

An  ass  being  tied  and  thrown, 
and  the  superior  maxillary 
branch  of  the  fifth  nerve  ex- 
posed, touching  this  nerve  gave 
acute  pain.  It  zvas  divided,  but 
no  change  took  place  in  the  mo- 
tion of  the  nostril ;  the  cartil- 
ages continued  to  expand  regu- 
larly in  time  with  the  other 
parts,  which  combine  in  the  act 
of  respiration.  If  the  same 
branch  of  the  fifth  be  divided 
on  the  opposite  side,  and  the 
animal  let  loose,  he  will  not  pick 
up  his  corn ;  the  power  of  ele- 
vating and  projecting  the  lip,  as 
in  gathering  food,  was  lost. 
He  will  press  the  mouth  against 
the  ground,  and  at  length  will 
lick  the  oats  from  the  ground 
with  his  tongue.  In  my  first 
experiment,  the  loss  of  motion 
of  the  lips  Tvas  so  obvious,  that 
it  was  thought  a  useless  cruelty 
to  cut  the  other  branches  of  the 
fifth— (pp.  412,  413). 


Experiments  on  the  nerves 
OF  the  f  ace, zvith  avicwto  ascer- 
tain the  uses  of  the  portio  dura. 

If  an  ass  be  thrown,  and  the 
portio  dura  be  cut  across  where 
it  emerges  upon  the  face,  before 
the  ear,  all  the  muscles  of  the 
face,  except  those  of  the  jaws, 
zcill  be  paralysed.  If  its  nos- 
trils be  confined  for  a  fezv  sec- 
onds, so  as  to  make  it  pant  and 
forcibly  dilate  the  nostrils  at 
each  inspiration,  and  if  the  por- 
tio dura  be  nozu  divided  on  one 
side  of  the  head,  the  motion  of 
the  nostril  of  the  same  side  will 
instantly  cease,  zuhile  the  other 
nostril  zvill  continue  to  expand 
and  contract  in  unison  zvith  the 
motions  of  the  chest. 

On  division  of  this  nerve,  the 
animal  will  give  no  sign  of 
pain ;  or  in  no  degree  equal  to 
what  results  from  dividing  the 
fifth  nerve. 

If  an  ass  be  tied  and  thrown, 
and  the  superior  maxillary 
branch  of  the  fifth  nerve  ex- 
posed, touching  this  nerve  gives 
acute  pain.  When  it  is  divided, 
no  change  takes  place  in  the 
motion  of  the  nostril ;  the  car- 
tilages continue  to  expand  reg- 
ularly in  time  with  the  other 
parts  which  combine  in  the  act 
of  respiration;  but  the  sensibil- 
ity is  entirely  lost.  If  the  same 
branch  of  the  fifth  be  divided 
on  the  opposite  side,  and  the 
animal  let  loose,  the  parts  will 
be  deprived  of  sensibility,  and 
he  will  not  pick  up  his  corn :  the 
power  of  elevating  and  project- 
ing the  lip,  as  in  gathering  food, 
zvill  appear  to  be  lost.  He  will 
press  the  mouth  against  the 
ground,  and  at  length  lick  the 
oats  from  the  ground  with  his 
tongue.  In  my  first  experi- 
ments the  loss  of  sensibility  of 
the  lips  zuas  so  obvious,  that  it 


52 


ROOTS   OF   THE   SPINAL   NERVES 


From  these  facts  we  are  en- 
titled to  conclude,  that  the  por- 
tio  dura  of  the  seventh  is  the 
respiratory  nerve  of  the  face ; 
that  the  motions  of  the  lips,  the 
nostrils,  and  the  velum  palati, 
are  governed  by  its  influence, 
when  the  muscles  of  these  parts 
are  in  associated  action  with  the 
other  organs  of  respiration — 
(p.  414). 


Of  the  functions  of  the 
trigeminus,  or  fifth  nerve, 
as  illustrated  by  these  ex- 
periments. 


was  thought  a  useless  cruelty  to 
cut  the  other  branches  of  the 
fifth — (p.  52). 

From  these  facts  we  are  en- 
titled to  conclude,  that  the  por- 
tio  dura  of  the  seventh  is  the 
nerve  of  motion  to  the  muscles 
of  the  forehead,  eyebrow,  eye- 
lids, nostril,  lips,  and  ear;  that 
is,  to  all  the  muscles  of  the  face 
except  those  of  mastication — 
that  it  is  the  respiratory  nerve 
of  the  face ;  that  the  motions  of 
the  lips,  the  nostrils,  and  the 
velum  palati,  are  governed  by 
its  influence,  when  the  muscles 
of  these  parts  are  in  associated 
action  with  the  other  organs  of 
respiration — (p.  54). 

Of  the  FUNCTIONS  OF  THE 
TRIGEMINUS,    OR   FIFTH    NERVE. 


Independently  of  the  differ- 
ence of  sensibility  in  these 
nerves,  there  was  exhibited,  in 
all  these  experiments,  a  wide 
distinction  in  their  powers  of 
exciting  the  muscles.  The 
slightest  touch  of  the  portio 
dura,  or  respiratory  nerve,  con- 
vulsed the  muscles  of  the  face, 
whilst  the  animal  gave  no  sign 
of  pain.  By  means  of  the 
branches  of  the  fifth  nerve,  it 
was  more  difficult  to  produce 
any  degree  of  action  in  the 
muscles,  although,  as  I  have 
said,  touching  the  nerve  gave 
great  pain — (p.  58). 


Independently  of  the  differ- 
ence of  sensibility  in  these 
nerves,  there  was  exhibited,  in 
all  these  experiments,  a  wide 
distinction  in  their  powers  of 
exciting  the  muscles.  The 
slightest  touch  of  the  portio 
dura,  or  respiratory  nerve,  con- 
vulsed the  muscles  of  the  face, 
whilst  the  animal  gave  no  sign 
of  pain.  By  means  of  the 
branches  of  the  fifth  nerve,  it 
zvas  not  possible  to  excite  the 
muscles,  if  the  trunk  of  the 
nerve  were  divided  behind  the 
part  bruised;  that  is  to  say,  if 
the  communication  with  the 
sensorium  zvere  cut  off — (p. 58). 


The  paper  from- which  the  above  extracts  are  made  does 
not  treat  directly  of  the  spinal  nen'es,  but  many  passages 
are  so  worded  in  the  reprint  as  to  make  it  appear  that  its 
author  recognized  fully  the  distinction  between  the  motor 


ROOTS   OF   THE   SPINAL   NERVES  53 

and  the  sensory  nerves  throughout  the  system;  and,  as  be- 
fore remarked,  it  has  been  referred  to  by  Shaw  and  others 
as  evidence  that  these  facts  were  well  known  before  the 
publication  of  Magendie's  experiments.  In  republishing 
a  paper  of  this  kind,  the  author  undoubtedly  had  a  right 
to  make  such  additional  explanations  and  such  corrections 
as  might  be  demanded  by  the  advanced  state  of  knowledge 
on  the  subject;  but  such  alterations  should  have  been  so 
introduced  as  to  be  distinguishable  from  the  original  mat- 
ter. Many  additions,  not  bearing  on  the  subject  under  con- 
sideration, have  not  been  quoted;  *  and  I  have  noted  some 
unimportant  alterations  so  as  not  to  destroy  the  sense  of 
the  extracts;  but  a  careful  comparison  of  some  of  the  pas- 
sages which  have  been  put  side  by  side  will  make  it  evident 
that  most  of  Sir  Charles  Bell's  definite  knowledge  regard- 
ing the  seat  of  motion  and  sensation  in  the  nervous  system 
was  acquired  after  the  first  publication  in  the  "  Philosoph- 
ical Transactions." 

In  the  first  extract,  in  speaking  of  a  branch  of  the  fifth, 
it  will  be  seen  that  Bell  confounds  the  two  properties  of 
motion  and  sensation;  but  he  corrects  this  error  in  the 
reprint.  He  again  speaks  of  this  nerve  as  receiving  roots 
from  the  medullary  process  of  the  cerebrum  and  the  cere- 
bellum; wdiich,  in  the  reprint,  he  calls  "  the  column  of  sensi- 
bility and  that  of  motion."  In  the  first  publication  he  calls 
the  portio  dura  simply  the  '*  respiratory  nerve  of  the  face;  " 
and  in  the  reprint  he  has  modified  his  phraseology,  and 
speaks  of  it  as  the  "  motor  and  respiratory  nerve  of  the 
face."  In  another  place  he  details  an  experiment  in  which 
the  superior  maxillary  branch  of  the  fifth  was  divided  in  an 
ass;  and  in  the  reprint  he  states  that  sensibility  was  entirely 
lost,  etc.,  but  does  not  mention  this  in  his  original  paper. 
He  also  says,  in  the  same  connection,  that  after  this  opera- 
tion '■'  the  loss  of  motion  of  the  lips  was  so  obvious,"  etc., 
and  in  the  reprint  he  has  it  that  "  the  loss  of  sensibility  of 
the  lips  was  so  obvious."  A  careful  study  of  the  first  mem- 
oir will  show  that  he  never  made  correct  applications  of 
the  terms  motor  and  sensory  with  reference  to  different 

*  The  alterations  from  the  original  publication  in  the  "  Philosophical  Trans- 
actions "  are  much  more  extensive  in  the  late  editions  of  the  work  on  the  nerves 
than  in  the  previous  issues.  In  an  edition  reprinted  in  this  country  (Washing- 
ton, 1833)  the  corrections  are  much  fewer. 


54  ROOTS   OF   THE   SPINAL   NERVES 

portions  of  the  nervous  system;  and  that  this  memoir  of 
1 82 1  added  nothing,  as  regards  the  discovery  of  the  func- 
tions of  the  roots  of  the  nerves,  to  the  paper  printed  in 
1811.* 

II 

REVIEW  OF  THE  CLAIMS  OF  MAGENDIE  TO  THE  DISCOVERY 
OF  THE  DISTINCT  PROPERTIES  OF  THE  ROOTS  OF  THE 
SPINAL   NERVES 

The  first  publications  of  rvlagendie  concerning  the  anat- 
omy and  the  functions  of  different  portions  of  the  nerv- 
ous system  appeared  in  the  "  Journal  de  physiologic,"  in 
1821.  In  the  first  volume  of  this  journal  is  a  notice  of  the 
researches  of  Charles  Bell  on  the  nerves  of  the  face,  with 
an  account  of  the  observations  of  Mr.  Shaw  on  the  same 
subject. f  Magendie  here  states  that  he  repeated  the  ex- 
periments of  Bell  with  MM.  Shaw  and  Dupuy  at  Alfort.:}: 
Magendie  had  not  at  that  time  received  the  memoir  of  Bell; 
but  in  a  succeeding  number  of  the  Journal  he  gives  a  full 
analysis  of  it.*  In  this  number,  also,  he  speaks  of  having 
repeated  the  experiments.  In  the  same  Journal  follows  a 
translation  of  the  experiments  of  Mr.  Shaw.|i  In  none  of 
these  publications  is  there  any  allusion  to  the  properties  of 
the  anterior  and  posterior  roots  of  the  spinal  nerves,  nor 
is  there  any  evidence  that  either  Bell,  Shaw  or  Magendie 
knew  anything  about  the  distinct  seat  of  motion  and  sensa- 
tion in  the  spinal  cord  and  the  spinal  nerves.'^ 

*  A  paper  by  Mr.  John  Shaw,  in  the  "  Medico-Chirurgical  Transactions," 
in  June,  1822,  some  months  before  Magendie's  experiments  were  published,  is 
said  to  contain  an  account  of  Bell's  views  of  the  nerves.  The  statements  here, 
however,  are  no  more  definite  than  the  quotations  which  I  have  made  from 
Bell's  original  writings. 

f  "  Recherches  anatomiques  et  physiologiques  sur  le  systeme  nerveux  ; " 
par  M.  Charles  Bell. — "Journal  de  physiologie,"  Paris,  1821,  tome  i.,  p.  384, 
et  seq. 

X  Loc.  cit.,  p.  387. 

*  "  Suite  des  recherches  anatomiques  et  physiologiques  sur  le  systeme  ner- 
veux," par  M.  Bell. — "Journal  de  physiologie,"  Paris,  1S22,  tome  ii.,  p.  66, 
et  seq. 

II  "  Experiences  sur  le  systeme  nerveux  ;  "  par  M.  Shaw.  Extrait  et  tra- 
duit  de  I'Anglais  par  M.  Cairns. — "Journal  de  physiologie,"  Paris,  1822,  tome 
ii.,  p.  77,  et  seq. 

^  In  the  same  volume  of  the  Journal  (p.  363),  Magendie  gives  an  account  of 
Bell's  observations  on  the  respiratory  nerves  of  the  chest,  which  were  presented 
to  the  "  Royal  Society,"  May  2,  1822. 


ROOTS    OF    THE    SPINAL    NERVES  55 

In  August,  1822  Magendie  published  his  first  experi- 
ments on  the  functions  of  the  roots  of  the  spinal  nerves."^ 
Unlike  any  of  the  experiments  performed  by  Bell  on 
the  spinal  nerves,  these  were  made  upon  living  animals. 
The  spinal  canal  was  opened,  and  the  cord,  with  the  roots 
of  the  nerves,  exposed.  The  posterior  roots  of  the  lumbar 
and  sacral  nerves  were  then  divided  upon  one  side  and  the 
wound  united  with  sutures.  The  result  of  this  ol^servation 
was  as  follows:  f 

"  I  thought  at  first  that  the  limb  corresponding  to  the  divided 
nerves  was  entirely  paralyzed;  it  was  insensible  to  pricking  and 
to  the  most  severe  pinching,  it  also  appeared  to  me  to  be  motionless ; 
but  soon,  to  my  great  surprise,  I  saw  it  move  in  a  very  marked  man- 
ner, although  the  sensibility  was  still  entirely  extinct.  A  second, 
a  third  experiment,  gave  me  exactly  the  same  result;  I  commenced 
to  regard  it  as  probable  that  the  posterior  roots  of  the  spinal  nerves 
might  have  functions  different  from  the  anterior  roots,  and  that 
they  were  more  particularly  devoted  to  sensibility."  ^ 

The  experiments  in  which  the  anterior  roots  were  di- 
vided were  no  less  striking: 

"  As  in  the  preceding  experiments,  I  only  made  the  division 
upon  one  side,  in  order  to  have  a  term  of  comparison.  One  can 
conceive  with  what  curiosity  I  followed  the  effects  of  this  division ; 
they  were  not  at  all  doubtful,  the  limb  was  completely  motionless 
and  flaccid,  while  it  preserved  a  marked  sensibility.  Finally,  that 
nothing  should  be  neglected,  I  divided  at  the  same  time  the  anterior 
and  the  posterior  roots ;  then  followed  absolute  loss  of  sensation  and 
of   motion."  * 

*  "  Experiences  sur  las  fonctions  des  racines  des  nerfs  rachidiens  ;  "  par 
F.  Magendie. — "  Journal  de  physiologie,"  Paris,  1822,  tome  ii.,  p.  276,  et  seq. 

f  The  original  of  the  important  passages  quoted  from  Magendie  is  given  in 
foot-notes,  and  the  translation  into  English  is  as  nearly  literal  as  possible. 

J  "  Je  crus  d'abord  le  membre  correspondant  aux  nerfs  coupes,  enti^rement 
paralyse  ;  il  etait  insensible  aux  piqures  et  aux  pression  les  plus  fortes,  il  me 
paraissait  aussi  immobile  ;  mais  bientot,  a  ma  grande  surprise,  je  le  vis  se  mou- 
voir  d'une  mani^re  tres  apparente,  bien  que  la  sensibilite  y  fut  toujours  tout-a- 
fait  eteinte.  Une  seconde,  un  troisi^me  experience,  me  donnerent  exactement 
le  meme  resultat ;  je  commenfais  a  regarder  comme  probable  que  les  racines 
posterieures  des  nerfs  rachidiens  pourraient  bien  avoir  des  fonctions  dififerentes 
des  racines  anterieures,  et  qu'elles  etaient  plus  particuli^rement  destinees  a  la 
sensibilite." — ("  Journal  de  physiologie,"  Paris,  1822,  p.  277.) 

*  "  Comme  dans  les  experiences  precedentes,  je  ne  fis  la  section  que  d'un 
seul  cote  d'avoir  un  terme  de  comparaison.  On  conceit  avec  quelle  curiosite  je 
suivis  les  effets  de  cette  section  ;  ils  ne  furent  point  douteux,  le  membre  etait 
completement  immobile  et  flasque,  tandis  qu'il  conservait  une  sensibilite  non 
equivoque.  Enfin,  pour  ne  rien  negliger,  j'ai  coupe  a  la  fois  les  racines  ante- 
rieures et  les  post^rieures  ;  il  y  a  eu  perte  absolue  de  sentiment  et  de  mouve- 
ment." — {Ibid.,  p.  278.) 


56  ROOTS    OF   THE   SPINAL   NERVES 

From  these  experiments  IMagendie  drew  the  following" 
conclusions: 

"  I  am  following  out  my  researches,  and  shall  give  a  more  de- 
tailed account  of  them  in  the  following  number ;  it  is  sufficient  for 
me  to  be  able  to  announce  at  present  as  positive,  that  the  anterior 
and  the  posterior  roots  of  the  nerves  which  arise  from  the  spinal 
cord  have  different  functions,  that  the  posterior  seem  more  par- 
ticularly devoted  to  sensibility,  while  the  anterior  seem  more  espe- 
cially connected  with  motion."  * 

In  the  second  note,  published  in  the  same  volume  of  the 
"  Journal  de  physiologic,"  Alagendie  exposed  and  irritated 
the  two  roots  of  the  nerves,  with  the  following  results: 

"  I  commenced  by  examining  in  this  regard  the  posterior  roots,, 
or  the  nerves  of  sensibility.  The  following  is  the  result  which  I 
observed:  on  pinching,  pulling,  or  pricking  these  roots,  the  animal 
manifested  pain ;  but  this  was  not  to  be  compared  as  regards  inten- 
sity with  that  which  was  developed  if  the  spinal  cord  was  touched,, 
even  lightly,  at  the  point  of  origin  of  the  roots.  Nearly  every 
time  that  the  posterior  roots  were  thus  stimulated,  contractions 
were  produced  in  the  muscles  to  which  the  nerves  were  distributed; 
these  contractions,  however,  are  not  well  marked,  and  are  infinitely 
more  feeble  than  when  the  cord  itself  is  touched.  When,  at  the 
same  time,  a  bundle  of  the  posterior  root  is  cut,  there  is  produced 
a  movement  in  totality  in  the  limb  to  which  the  bundle  is  distributed. 

"  I  repeated  the  same  experiments  on  the  anterior  roots,  and  I 
obtained  analogous  results,  but  in  an  opposite  sense ;  for  the  con- 
tractions excited  by  the  contusion,  the  pricking,  etc.,  are  very  forci- 
ble, and  even  convulsive,  while  the  signs  of  sensibility  are  hardly 
visible.  These  facts  are,  then,  confirmatory  of  those  which  I  have 
announced;  only  they  seem  to  establish  that  sensation  is  not  exclu- 
sively in  the  posterior  roots,  any  more  than  motion  in  the  anterior 
roots.  Nevertheless,  a  difficulty  may  arise.  When,  in  the  preceding" 
experiments,  the  roots  had  been  cut,  they  were  attached  to  the  spinal 
cord.  Might  not  the  disturbance  communicated  to  the  cord  be  the 
real  cause  either  of  the  contractions  or  of  the  pain  which  the  ani- 
mals experienced  ?  To  remove  this  doubt,  I  repeated  the  experi- 
ments after  having  separated  the  roots  from  the  cord ;  and  I  must 
say  that,  except  in  two  animals,  in  which  I  saw  contractions  when 
I  pinched  or  pulled  the  anterior  and  posterior  roots,  in  all  the  other 
instances  I  did  not  observe  any  sensible  effect  of  irritation  of  the 
anterior  or  posterior  roots  thus  separated  from  the  cord."  f 

*  "  Je  poursuis  ces  recherches  et  j'en  donnerai  un  recit  plus  detaille  dans  le 
prochain  numero  ;  il  me  suffit  de  pouvoir  avancer  aujourd'hui  comme  positif, 
que  les  racines  anterieures  et  les  posterieures  des  nerfs  qui  naissent  a  la  moelle 
epin^re,  ont  des  fonctions  dififerentes,  que  les  posterieures  paraissent  plus  par- 
ticulierement  destinees  a  la  sensibilite,  tandis  que  les  anterieures  semblent  plus 
specialement  liees  avec  la  mouvement." — [Ibid.,  p.  279.) 

f  "  J'ai  commence  par  examiner  sous  ce  rapport  les  racines  posterieures,  ou 
les   nerfs   du    sentiment.     Voici   ce    que  j'ai   observe  :  en    pinjant,    tiraillant» 


ROOTS    OF   THE   SPINAL    NERVES  57 

Magendie  then  goes  on  to  say  that  when  he  pubHshed 
the  note  in  the  preceding  number  of  the  Journal  he  sup- 
posed that  he  was  the  first  who  had  thought  of  cutting  the 
roots  of  the  spinal  nerves;  but  he  was  soon  undeceived  by 
a  letter  from  Mr.  Shaw,  who  stated  that  Bell  had  divided 
the  roots  thirteen  years  before.  Magendie  afterward  re- 
ceived from  Mr.  Shaw  a  copy  of  Bell's  essay  ("  Idea  of  a 
New  Anatomy  of  the  Brain"),  and,  as  will  be  seen  by  the  fol- 
lowing extract,  gave  Bell  full  credit  for  all  his  observations. 

"  It  is  seen  by  this  quotation  from  a  work  which  I  could  not  be 
acquainted  with,  inasmuch  as  it  had  not  been  published,  that  Mr. 
Bell,  led  by  his  ingenious  ideas  concerning  the  nervous  system,  was 
very  near  discovering  the  functions  of  the  spinal  roots ;  still  the 
fact  that  the  anterior  are  devoted  to  movement,  while  the  posterior 
belong  more  particularly  to  sensation,  seems  to  have  escaped  him; 
it  is,  then,  to  having  established  this  fact  in  a  positive  manner  that 
I  must  limit  my  pretensions."  * 

Such  are  the  experiments  by  w-hich  the  properties  of  the 
roots  of  the  spinal  nerves  were  discovered.  From  that  time 
the  fact  took  its  place  in  science  that  the  posterior  roots 

piquant  ces  racines,  Tanimal  temoigne  de  la  douleur  ;  mais  elle  n'est  point  k 
comparer  pour  I'intensite  avec  celle  que  se  developpe  si  Ton  louche,  meme 
legerement,  la  moelle  epinere  a  Tendroit  ou  naissent  ces  racines.  Presque 
toutes  les  fois  que  Ton  excite  ainsi  les  racines  posterieures  il  se  produit  des  con- 
tractions dans  les  muscles  ovi  les  nerfs  se  distribuent  ;  ces  contractions  sont 
cependant  peu  marquees,  et  infiniment  plus  faibles  que  si  on  touche  la  moelle 
elle-meme.  Quand  on  coupe  a  las  fois  un  faisceau  de  racine  posterieure,  il  se 
produit  un  mouvement  de  totalitc  dans  le  membre  ou  le  faisceau  va  se  rendre. 

"  J'ai  repete  les  memes  tentatives  sur  les  faisceaux  anterieurs,  et  j'ai  obtenu 
de  resultats  analogues,  mais  en  sens  inverse  ;  car  les  contractions  excitees  par 
le  pincement,  la  piqure,  etc.,  sont  tres-fortes  et  meme  convulsives,  tandis  que 
les  signes  de  sensibilite  sont  a  peine  visibles.  Ces  faits  sont  done  confirmatifs 
de  ceux  que  j'ai  annonces  ;  seulement  ils  semblent  etablir  que  le  sentiment 
n'est  pas  exclusivement  dans  les  racines  posterieures,  non  plus  que  le  mouve- 
ment dans  les  anterieurs.  Cependant  une  difficulte  pouvoit  s'elever.  Quand, 
dans  les  experiences 'que  precedent,  les  racines  ont  ete  coupees,  elles  etaient 
continues  avec  la  moelle  epinere  :  I'ebranlement  communique  k  celle-ci  ne 
serait-il  pas  la  veritable  origine  soit  des  contractions,  soit  de  la  douleur  qu'ont 
epreuves  les  animaux  ?  Pour  lever  ce  doute,  j'ai  refait  les  experiences  apres 
avoir  separe  les  racines  de  la  moelle  ;  et  je  dois  dire  qu'excepte  sur  deux  ani- 
maux, ou  j'ai  vu  des  contractions  quand  je  pin9ais  ou  tiraillais  les  faisceaux 
anterieurs  et  posterieurs,  dans  tous  les  autres  cas  je  n'ai  obsei-ve  aucun  effet 
sensible  de  I'irritation  des  racines  anterieures  ou  posterieures  ainsi  separees  de 
la  moelle." — {Ibid.,  p.  368.) 

*  "On  voit  par  cette  citation  d'un  ouvrage  que  je  ne  pouvois  connaitre, 
puisqu'il  n'a  point  ete  publie,  que  M.  Bell,  conduit  par  ces  ingenieuses  idees 
sur  la  systeme  nerveux,  a  ete  bien  pres  de  decouvrir  les  fonctions  des  racines 
spinales  ;  toutefois  le  fait  que  les  anterieures  sont  destinees  au  mouvement, 
tandis  que  les  posterieures  appartiennent  plus  particulierement  au  sentiment, 
parait  lui  avoir  echappe  :  c'est  done  a  avoir  etabli  ce  fait  d'une  maniere  positive 
que  je  dois  borner  mes  pretentions." — {Ibid.,  p.  371.) 


58  ROOTS    OF    THE    SPINAL    NERVES 

are  for  sensation  and  the  anterior  for  motion.  Some  dis- 
cussion has  arisen  as  to  whether  the  anterior  roots  do  not 
possess  a  certain  degree  of  sensibihty,  called  recurrent  sen- 
sibility, and  this  question  has  engaged  the  attention  of  phys- 
iologists with  a  few  years;  *  but  the  distinct  functions  of 
the  two  roots  have  never  been  doubted.  It  has  already  been 
seen  what  use  Bell  made  of  these  facts  in  late  editions 
of  his  work  on  the  nervous  system.  Before  the  days  of 
anesthetics,  exposing  the  roots  of  the  nerves  in  the  dog 
was  very  laborious,  and  painful  to  the  animal,  and  the  dis- 
turbances produced  by  so  serious  an  operation  interfered 
somewhat  with  the  effects  of  irritation  of  the  different  roots. 
But  now  that  the  canal  may  be  opened  without  pain  to  the 
animal,  the  experiments  are  much  more  satisfactory  and 
have  often  been  repeated  by  physiologists.  I  have  fre- 
quently, indeed,  demonstrated  the  properties  of  the  roots 
of  the  nerves  in  public  teaching.f 

Although,  as  has  been  seen,  almost  all  physiological 
writers,  even  in  France,  regarded  Bell  as  the  real  discov- 
erer, Magendie  continued  to  claim  that  he  first  positively 
ascertained  the  seat  of  motion  and  sensation  in  the  spinal 
nerves.  In  1823,  after  reiterating  his  statements  in  regard 
to  the  nerves,  he  extended  his  researches  to  the  cord  itself, 
and  demonstrated  that  the  anterior  columns  are  motor  and 
the  posterior  columns  sensory. :{:  In  all  his  subsequent 
publications  the  same  statements  are  made.* 

*  Bernard,  "  Le9ons  sur  la  physiologic  et  la  pathologie  du  systeme  ner- 
veux."  Paris,  1858,  tome  i.,  p.  20,  et  seq.  Even  Bernard,  a  pupil,  and  for  a 
long  time  the  "  preparateur  "  for  Magendie,  at  one  time  seemed  to  regard  Sir 
Charles  Bell  as  the  discoverer  of  the  functions  of  the  roots  of  the  spinal  nerves 
(ibid.,  p  25,  and  "  Lecons  sur  les  effets  des  substances  toxiques  et  medica- 
menteuses."  Paris,  1857,  p.  20)  ;  in  a  late  worlc,  however,  in  which  this  whole 
subject  is  reviewed,  the  claims  of  Magendie  to  the  discovery  are  fully  recog- 
nized (Bernard,  "  Rapport  sur  les  progres  et  la  marche  de  la  physiologic  gene- 
rale  en  France."  Paris,  1867,  pp.  12  and  154).  Bernard  states  that  he  was 
unable  to  obtain  the  original  memoir  of  Bell,  printed  in  l8ri,  but  finally  pro- 
cured an  exact  copy,  which  is  probably  the  reprint  of  1839.     {IHd.,  p.  155.) 

f  Flint,  "  Experiments  on  the  Recurrent  Sensibility  of  the  Anterior  Roots 
of  the  Spinal  Nerves." — "  New  Orleans  Medical  Times,"  1861,  p.  21,  et  seq. 

At  the  time  that  this  paper  was  written,  I  had  not  had  an  opportunity  of 
consulting  the  original  memoir  of  Sir  Charles  Bell,  and,  with  others,  I  regarded 
him  as  the  discoverer  of  the  functions  of  the  roots  of  the  nerves.  I  have  also 
had  occasion  to  modify  the  views  therein  expressed  concerning  the  recurrent 
sensibility  of  the  anterior  roots. 

\  Magendie,  "  Note  sur  le  siege  du  mouvement  et  du  sentiment  dans  le  moel- 
le  epinere." — "  Journal  de  physiologic,"  Paris,  1823,  tome  iii.,  p.  153,  et  seq. 

*  Desmoulins  et  Magendie,  "Anatomic  des  systemes  nerveux  des  animaux 


ROOTS    OF    THE    SPINAL   NERVES  59 

Shaw,  in  his  "  Narrative,"  states  that  in  1822  Magen- 
die  "  admitted  that  the  experiments  on  the  roots  of  the 
spinal  nerves,  which  he  had  claimed  as  original,  had  been 
performed  many  years  before  by  Sir  Charles  Bell."  *  This 
is  not  correct;  and  I  have  already  quoted  in  full  the  passage 
in  which  Magendie  gives  Bell  full  credit  for  what  he  had 
done,  but  expressly  states  that  the  fact  that  the  anterior 
roots  preside  over  movements  and  the  posterior  over  sensa- 
tion seems  to  have  escaped  him.  Shaw  also  quotes  Des- 
moulins  and  Magendie  as  admitting  '*  that  there  is  no  ab- 
solute distinction  between  the  functions  possessed  by  the 
two  roots;  "  f  but  in  doing  this  he  translates  the  expres- 
sion into  English  incorrectly.  In  the  passage  referred  to, 
it  is  stated  that  "  L'isolement  des  deux  proprietes  dans 
chacun  des  deux  ordres  de  racines,  n'est  done  pas  absolu," 
which  simply  means  that  the  motor  roots  are  not  absolute- 
ly without  sensibility  and  the  sensory  roots  are  not  abso- 
lutely devoid  of  motor  properties. 

The  experiments  of  Magendie  made  in  1822  must  stand 
without  further  question  as  the  first  to  demonstrate  the  true 
properties  of  the  two  roots  of  the  spinal  nerves;  and  be- 
fore the  publication  of  these  experiments  no  physiologist 
had  a  correct  idea,  theoretical  or  experimental,  of  the  seat 
of  motion  and  sensation  in  these  nerves.  There  can  be  no 
doubt  that  the  honor  of  this  discovery  belongs  exclusively 
to  Magendie. 

CONCLUSION 

In  its  bearing  on  future  knowledge  in  physiology,  no 
discovery  can  be  regarded  as  equal  to  that  of  the  circula- 
tion of  the  blood,  by  Harvey.  But  since  this,  which  marks 
a  great  epoch  in  science,  there  has  been  nothing  so  impor- 
tant as  the  location  of  the  properties  of  motion  and  sensa- 
tion in  different  portions  of  the  cerebro-spinal  nervous  sys- 
tem. From  this  dates  nearly  all  positive  knowledge 
concerning  the  functions  of  this  system.  For  many  years 
the  credit  of  this  great  discovery  has  been  either  indefinitely 
or  incorrectly  assigned  by  the  great  majority  of  physio- 
logical writers,  simply  because  few  had  an  opportunity  of 
consulting  for  themselves  the  original  pamphlet  in  which 

k  vertebres."  Paris,  1825,  tome  ii.,  p.  777.  Magendie,  "  Pre'cis  elementaire  de 
physiologic,"  deuxieme  edition.  Paris,  1825,  tome  i.,  pp.  167,  216,  et  quatrieme 
edition,  1836,  tome  i.,  pp.  200,  266.  *  0/>.  cit.,  p.  156.         f  Op.  cit.,  p.  168. 


6o  ROOTS    OF   THE    SPINAL    NERVES 

the  first  observations  of  Charles  Bell,  the  reputed  discover- 
er, are  contained.  If  Bell  or  his  defenders  had  published 
this  memoir,  which  is  only  twenty  pages  in  length,  entire, 
he  would  undoubtedly  have  received  full  credit  for  all  the 
advances  which  he  really  made  in  the  physiology  of  the 
nervous  system,  and  no  injustice  would  have  been  done  to 
others.  Having  obtained  a  complete  and  authentic  reprint 
of  the  original  memoir,  I  have  endeavored  to  review  it  care- 
fully and  dispassionately,  quoting  all  the  passages  which 
bear  upon  the  functions  of  the  nerves,  in  the  hope  of  being 
able  to  settle  forever  the  respective  claims  of  Sir  Charles 
Bell  and  Magendie  to  this  discovery.  From  a  review  of 
this  and  other  papers  l)y  Walker,  Bell,  Shaw  and  Magendie,. 
the  following  conclusions  are  inevitable: 

Like  many  great  discoveries,  the  idea,  and  the  experi- 
ments by  which  it  was  carried  out  and  elaborated,  did  not 
emanate  from  a  single  mind. 

In  1809,  Alexander  Walker  proposed  for  the  first  time 
the  theory  that  the  properties  of  motion  and  sensation  in 
the  mixed  nerves  were  derived  from  the  two  roots  by  which 
they  take  their  origin  from  the  spinal  cord.  This  idea  w^as 
entirely  theoretical;  and  sensation  was  assigned  to  the  an- 
terior root  and  motion  to  the  posterior  root. 

In  181 1,  Charles  Bell,  who  was  the  first  to  experiment 
on  the  spinal  nerves  in  animals  recently  killed,  ascertained 
by  experiment  that  the  posterior  roots  of  the  spinal  nerves 
had  hardly  any  motor  properties.  He  ascribed  both  mo- 
tion and  sensation  to  the  anterior  roots  and  supposed  that 
the  posterior  roots  presided  over  w-hat  are  now  known  as 
the  vegetative,  or  organic  functions.  He  knew  nothing 
about  the  sensibility  of  the  posterior  roots. 

In  1822,  F.  Magendie,  who  was  the  first  to  experiment 
on  the  spinal  nerves  in  living  animals,  ascertained  by  ex- 
periment that  the  anterior  roots  of  the  spinal  nerves  pre- 
sided over  movement  and  the  posterior  roots  over  sensa- 
tion. He  believed  these  to  be  distinct  functions  of  these 
roots,  but  he  thought  at  that  time  that  the  anterior  roots 
might  be  slightly  sensitive  and  the  posterior  roots  might 
possess  some  motor  properties. 

From  the  experiments  of  Magendie  dates  all  positive 
knowledge  of  the  physiological  properties  of  the  two  roots 
of  the  spinal  ner\^es. 


V 

EXPERIMENTAL  RESEARCHES  ON  POINTS 
CONNECTED  WITH  THE  ACTION  OF  THE 
HEART   AND    WITH    RESPIRATION 

Published  in  the  "  American  Journal  of  the  Medical  Sciences  "  for  October, 

1 86 1. 

It  is  not  intended  in  this  paper  to  take  up  all  points 
•connected  with  either  of  the  functions  which  will  come  un- 
■der  consideration.  This  of  course  would  be  inconsistent 
wdth  its  scope;  for  many  are  so  demonstrable  and  now  so 
well  established  that  their  consideration  here  would  be  a 
mere  recapitulation  of  facts  well  known  and  universally 
admitted.  It  is  rather  my  object  to  present  some  original 
•experiments  by  which  I  hope  to  elucidate  points  which  are 
yet  subjects  of  dispute  among  physiologists  and  which, 
in  my  opinion,  cannot  be  settled  by  argument  alone,  but 
are  capable  of  being  brought  under  direct  obsen^ation 
and  if  established  can  be  made  subjects  of  actual  demon- 
stration. Some  functions  can  not  as  yet  be  disclosed  to 
the  senses  in  their  natural  operation;  but  others,  which 
are  connected  with  questions  here  to  be  considered,  re- 
quire only  correct  description  to  serve  as  facts  from 
which  each  inquirer  may  make  his  own  deductions.  For 
the  understanding  of  those  processes  which  can  easily  be 
described  and  about  which  there  can  be  no  mistake,  noth- 
ing usually  is  necessary  but  simple  observation;  but  there 
are  others,  more  delicate  and  obscure,  which  different  ex- 
perimenters see  in  different  ways.  In  the  investigations 
into  their  phenomena  one  should  strive  to  perfect  methods 
of  observation,  to  devise  means  by  which  all  confusing 
circumstances  may  be  removed,  to  invent  instruments 
which  will  make  them  more  prominent,  so  that  any  ob- 
server, willing  to  take  the  trouble  to  look  for  himself,  can 
see  and  interpret  them  in  but  one  way.     This  is  no  less  a 

6i 


62    ACTION   OF   THE    HEART   AND   RESPIRATION 

desideratum  in  physiological  than  in  pathological  investi- 
gations; and  means  of  physical  exploration  should  be 
sought  which  will  be  to  the  physiologist  what  the  stetho- 
scope, the  speculum,  the  ophthalmoscope  and  our  many 
modern  exploring  instruments  are  to  the  pathologist.  Ob- 
stetricians might  differ  in  regard  to  conditions  of  the  os 
uteri,  exploring  only  by  the  touch,  when  the  speculum,  ex- 
posing the  parts  to  the  eye,  would  leave  no  room  for  dis- 
cussion; auscultators,  listening  with  the  naked  ear  through 
the  clothing  of  a  patient,  might  dispute  about  sounds  heard 
within  the  thorax,  when  they  would  agree  if  a  stethoscope 
were  applied  to  the  naked  chest.  I'hus,  perfected  appa- 
ratus enables  the  chemist  and  physiologist  to  demonstrate 
facts  that  would  be  obscure  with  less  certain  means  of  in- 
vestigation. Many  points  in  the  physiology  of  the  heart 
and  of  respiration  are  yet  undecided;  and  it  is  by  removing 
some  sources  of  self-deception  in  the  simple  observation 
of  phenomena  and  by  multiplying  demonstrable  facts,  the 
only  true  basis  of  general  deductions,  that  I  have  endeav- 
oured to  go  a  step  beyond  what  is  already  known  and  es- 
tablished. 

The  questions  which  I  shall  take  up  in  this  essay  are, 
with  reference  to  the  heart: 

First:  Does  the  organ  shorten  or  elongate  during  its 
ventricular  systole,  or  contraction? 

Second:  How  far  is  it  possible  to  determine  the  cause 
of  its  regular  and  periodic  action? 

Third:  What  are  some  of  the  causes  of  arrest  of  the 
action  of  the  heart? 

Fourth:  What  is  the  mechanism  of  some  of  the  nervous 
influences  over  the  action  of  the  heart? 

Fifth:  What  is  the  mechanism  of  the  action  of  the 
valves  which  guard  the  orifices  of  the  heart? 

And,  in  regard  to  respiration:  What  is  the  cause,  and 
w^here  is  the  seat  of  the  impression,  or  "  besoin  de  respirer," 
which  is  conveyed  to  the  respiratory  centre  and  which  ex- 
cites the  action  of  the  muscles  of  inspiration? 

These  questions  have  either  never  been  fully  under- 
stood by  physiologists  or  are  now  explained  in  a  contra- 
dictory manner  in  the  various  systematic  physiological 
treatises. 


ACTION    OF   THE    HEART   AND    RESPIRATION    6^ 

It  was  with  the  hope  of  contributing  something  to  the 
further  ehicidation  of  these  obscure  and  disputed  points 
that  the  experiments  which  form  the  basis  of  this  paper 
have  been  undertaken. 

Changes  in  Consistence,  Position  and  Form  of 
THE  Heart  during  its  Action. — In  regard  to  the  move- 
ments and  action  of  the  heart,  there  is  manifestly  but  one 
correct  mode  of  study,  and  that  is  the  one  which  led  Har- 
vey to  make  the  discovery  of  the  circulation  of  the  blood. 
This  method  is  to  expose  the  heart  in  living  animals  during 
its  action  and  observe  its  movements.  This  may  be  done 
in  various  animals  and  in  different  ways.  It  is  easy  to  ob- 
serve the  heart  in  action  in  the  cold-blooded  animals,  by 
simply  removing  the  anterior  walls  of  the  thorax;  and  its 
contractions  will  continue  for  a  long  time  after  such  an 
operation  and  even  after  the  organ  has  been  entirely  sepa- 
rated from  the  body.  Such  observations  give  a  great  deal 
of  information  but  are  made  more  valuable  when  compared 
with  phenomena  observed  in  warm-blooded  animals,  in 
which  the  heart  resembles  the  corresponding  organ  in 
man.  In  operating  upon  the  heart  of  these  animals,  such 
as  dogs,  cats,  sheep  or  horses,  it  is  necessary  to  keep  up 
artificial  respiration,  as  this  function  can  not,  of  course,  be 
performed  by  the  animal  after  the  thorax  has  been  opened. 
Here  it  is  convenient  as  well  as  humane  to  abolish  sensi- 
bility by  some  means  which  will  not  interfere  with  the 
heart's  action.  This  may  be  done  by  crushing  the  medulla 
oblongata  in  such  a  way  as  to  avoid  hemorrhage,  as  done 
by  Erichsen  and  Pavy,  of  London;  by  stunning  the  ani- 
mal with  a  blow  upon  the  head,  as  done  by  Drs.  Pennock 
and  Moore;  by  decapitation  and  ligature  of  the  vessels  of 
the  neck,  as  done  by  Legallois;  by  inoculation  with  curara 
or  by  the  administration  of  ether  or  chloroform,  which  are 
the  most  convenient  methods  and  those  now  most  com- 
monly employed  by  physiologists.  The  experiments  which 
I  have  made  have  been  performed  upon  animals  rendered 
insensible  by  curara  or  ether;  and  I  have  been  accustomed 
to  operate  in  the  following  way: 

The  animal,  preferably  a  good-sized  dog,  is  first  poi- 
soned with  curara  by  injecting  about  a  grain  of  this  sub- 
stance into  the  subcutaneous  areolar  tissue  or  is  completely 


64    ACTION    OF    THE    HEART    AND    RESPIRATION 

etherized.  If  poisoned  with  curara,  its  cllects  are  watched, 
and  in  ten  to  thirty  minutes  the  dog  comes  under  its  in- 
lluence;  more  readily,  if  he  is  made  to  move  about.  If 
ether  is  used,  he  is  rendered  insensible  in  the  ordinary  way. 
The  trachea  is  then  opened  and  the  nozzle  of  a  bellows  is 
introduced  for  the  purpose  of  keeping-  up  artificial  respi- 
ration. An  incision  is  then  made  in  the  median  line  from 
the  top  of  the  sternum  to  a  point  a  little  below  the  ensi- 
form  cartilage,  through  the  skin,  fascia  and  fat.  The  next 
step  is  to  cut  through  the  superficial  muscles  the  whole 
length  of  the  sternum  on  each  side,  about  an  inch  from 
the  median  line,  down  to  the  costal  cartilages,  and  then  to 
tear  away  the  muscles  from  the  chest,  exposing  the  ribs. 
The  next  step,  after  having  exposed  the  chest  in  this  man- 
ner, is  to  saw  through  the  sternum  in  the  median  line,  open- 
ing into  the  thoracic  cavity;  then  to  hold  open  the  chest 
by  sticks,  or  what  is  more  convenient,  to  cut  across  the 
ribs  on  each  side  with  a  pair  of  strong  cutting  pliers,  turn 
back  the  anterior  walls  of  the  thorax  and  retain  them  in 
that  position  by  a  strong  ligature  passed  under  the  back  of 
the  animal  and  firmly  tied.  In  this  way,  the  lungs,  which 
are  regularly  inflated  with  the  bellows,  are  exposed  and  be- 
tw'een  them  is  seen  the  heart  enclosed  in  its  pericardium. 
The  pericardium  may  then  be  removed  by  slitting  it  up  and 
cutting  it  away  from  its  attachments  at  the  base  of  the 
heart,  w^hich  may  then  be  observed  in  the  natural  perform- 
ance of  its  functions. 

When  the  heart  of  a  dog  is  exposed  in  this  way,  one  of 
the  most  constant  effects  is  an  increase  in  the  rapidity  of  its 
contractions.  The  pulse  of  a  dog  is  always  irregular  in  a 
state  of  health,  varying  between  lOO  and  120  beats  in  the 
minute.  When  the  heart  is  exposed  its  pulsations  become 
more  frequent,  sometimes  numbering  200  to  250. 

The  phenomena  which  are  observed  in  connection  with 
the  contraction  of  the  ventricles  are: 

I.  Hardening. — This  is  a  phenomenon  constantly  at- 
tending muscular  contraction.  It  was  described  by  Har- 
vey, who  proved  that  it  took  place  during  contraction  of 
the  ventricles,  by  introducing  a  small  canula  through  the 
walls  of  the  left  ventricle,  applying  the  hand  to  the  heart 
and  noticing  that  the  hardening  took  place  when  a  jet  of 
blood  was  forced  through  the  canula.     Nearly  all  physio- 


ACTION    OF    THE    HEART    AND    RESPIRATION    65 

logical  authors  are  agreed  on  this  point,  although  Dr. 
Wood,  late  of  the  University  of  Pennsylvania,  was  of  the 
opinion  that  the  heart  hardens  during  the  diastole.  I  have 
repeatedly  verified  the  fact  that  the  heart  hardens  during 
the  systole  by  repeating  the  experiment  of  Harvey.  One 
who  examines  the  heart  in  action  can  hardly  be  mistaken 
in  regard  to  this  point. 

II.  Tilting  Upwards  of  the  Point  of  the  Heart 
AND  Locomotion  of  the  Apex  from  Left  to  Right. — 
About  this  phenomenon  there  is  no  difference  of  opinion. 
It  can  easily  be  observed  in  vivisections,  and  this  movement 
would  be  expected  from  the  spiral  and  oblique  course  of 
the  superficial  fibres  of  the  heart  from  right  to  left,  arising 
at  the  base  and  inserted,  as  it  were,  into  the  apex,  which 
is  free. 

III.  Twisting  from  Left  to  Right. — This  can  be  ob- 
served by  examining  the  apex  of  the  heart.  It  is  univer- 
sally admitted  by  physiologists  and  is  explained  by  the 
spiral  course  of  the  fibres  from  right  to  left.  This  phe- 
nomenon, like  the  preceding,  I  have  repeatedly  ob- 
served. 

IV.  Elongation  of  the  Ventricles. — This  change 
in  the  length  of  the  ventricles  is  denied  by  modern  French, 
English  and  German  physiologists,  who  seem  all  to  agree 
that  Harvey  was  wrong  in  this  part  of  his  description  of 
the  action  of  the  heart.  Harvey,  Vesalius,  Riolan,  Fon- 
tana,  Borelli.  Winslow  and  Oueye  contended  for  the  elon- 
gation of  the  organ  during  its  systole;  but  this  view  was 
•combated  by  Steno,  Lancisi,  Bassuel  and  Haller.  It  seems 
to  me  that  the  prevalence  of  the  opinion,  at  the  present 
■day,  that  the  heart  shortens  during  systole  can  be  attributed 
in  great  measure  to  the  weight  of  the  opinion  of  Haller. 
I  am  fortunate  in  having  an  opportunity  of  referring  to  an 
edition  of  his  original  works,  published  in  1757,  and  could 
not  but  be  struck  with  its  similarity  in  views,  in  arguments, 
and  sometimes  even  in  actual  mode  of  expression,  when 
treating  of  the  change  in  the  length  of  the  heart  during  the 
systole,  with  the  works  on  physiology  which  are  now  used 
as  text-books,  especially  those  by  French  authors. 

Haller  bases  his  views  on  his  own  experiments  upon 
a  case  of  ectropy  of  the  heart  ("  Denique  in  puero,  cui  cor 
•extra  pectus  propendebat,  cor  in  diastole  longius,  et  in  sys- 

5 


66    ACTION    OF    THE    HEART    AND    RESPIRATION 

tole  brevius  factum  est,  perinde  ut  in  l)estiis  videnuis  "  *) 
and  on  an  argument  of  Bassuel.  This  last  argument  against 
the  elongation  of  the  heart  is  employed  by  many  physiolo- 
gists of  the  present  day.  Haller,  after  stating  the  views  and 
arguments  of  Vesalius,  Riolan  and  others,  says: 

"  Varia  nupcrrimi  scriptores  reposuerunt.  Et  quidem  CI.  Bas- 
suel ad  argumentum  a  valvulis  venosis  repetitum  rcspondit,  earum 
fabricam  contra  adversaries  facere.  Si  enim  in  systole  cordis  mu- 
cro  a  basi  recideret,  tunc  certe  sequeretur,  ut  adtractis  ad  apicem 
funiculis,  valvulse  in  cordis  caveam  deductae  ostium  aperirent,  san- 
guinique  venoso  earn  viam  referarent,  quam  utique  clausam  esse 
oportet,  dum  cor  contrahitur  Mihi  vero  videtur,  valvulas  quidem 
venosas  eo  tempore  a  sanguine  versus  aures  repulso  extrorsum, 
inque  aurium  cavitates  cessuras,  nisi  a  musculis  suis  papillaribus, 
eo  ipso  tempore  se  decurtantibus,  retinerentur,  inque  ventriculum 
reducerentur. 

"  Aliud  experimentum  addidit  CI.  Bassuel ;  cor  nempe  aqua  re- 
plevit,  viditque,  dum  brevius  fiebat,  aquam  expelli."  f 

I  have  exposed  thus  fully  the  views  of  Haller  on  this 
subject,  because  of  the  commanding  influence  he  so  long 
exercised  in  the  physiological  world,  and  especially  be- 
cause, on  this  point,  late  authors  seem  to  have  followed 
him  so  closely.  In  addition  it  may  not  be  uninteresting 
to  cite  a  few  of  the  authorities  who  favor  the  shortening  of 
the  heart  during  its  systole. 

Todd,  in  the  article  on  the  heart  in  the  "  Cyclopedia  of 
Anatomy  and  Physiology,"  speaking  of  the  organ  during 
its  systole,  says:  "  In  all  warm-blooded  animals,  at  least, 
it  becomes  shortened." 

Carpenter,  in  the  ''  Principles  of  Human  Physiology,"' 
London,  1855,  page  226,  says: 

"  During  their  contraction,  the  form  of  the  ventricles  undergoes 
a  very  marked  change,  the  apex  of  the  heart  being  drawn  up 
towards  its  base,  and  its  whole  shape  becoming  much  more  glob- 
ular." 

Kirkes,  "  Handbook  of  Physiology,"  in  speaking  of  the 
action  of  the  ventricles,  says: 

"  They  contract  much  more  slowly  than  the  auricles,  and  simul- 
taneously in  every  part,  the  whole  wall  of  each  ventricle  being 
drawn  up  uniformly  towards  the  origin  of  the  artery  at  its  base, 
diminishing  the  cavity  in  every  diameter,  but  especially  in  length, 
so  that  the  heart  assumes  a  shorter  and  more  globular  form  than  it 
had  in  the  relaxed  and  distended  state  of  the  ventricles." 

*  "  Elementa  Physiologiae,"  tome  i.,  p.  392.  +  Ibid.,  tome  i.,  p.  391. 


ACTION    OF   THE    HEART   AND    RESPIRATION    67 

Among  the  French  authors  is  Beclard,  "  Traite  de  phys- 
iologie,"  Paris,  1856: 

"  Le  Raccourissement  general  de  I'organe,  au  moment  de  la 
contraction  des  oreillettes,  est  assez  limite.  Son  plus  grand  rac- 
courssement  coincide  avec  la  contraction  des  ventricles,  qui  I'em- 
porte  par  dimensions  les  oreillettes  "...  "  chez  quelques  animaux, 
le  raccourissement  suivant  la  verticale  est  moins  prononce  que  le 
raccourissement  sur  I'horizontale,  ce  qui  a  fait  penser  faussement 
a  quelques  observateurs  que  le  cceur  s'allonge  pendant  la  systole 
ventriculaire." 

Richerand,  "  Elements  de  physiologie."  tome  i.,  p.  478, 
says : 

"  D'apres  cela,  il  est  evident  que  le  coeur  se  raccourcit,"  meaning 
during  the  systole. 

Beraiid,  "  Elements  de  physiologie,"  revus  par  Ch. 
Robin,  tome  ii.,  p.  zyy,  says,  speaking  of  the  systole: 

"  Le  sommet  des  ventricles  se  rapproche  de  la  base  et  du  som- 
met,  il  suit  de  la  que  la  coeur  se  raccourcit." 

Magendie,  "  Precis  elementaire  de  physiologie,"  tome 
ii.,  p.  395,  says: 

"  Les  partisans  de  I'allongement  ne  persistent  plus ;  mais  il  re- 
stait  a  demontrer  comment,  les  ventricules  se  raccourissant,  le  coeur 
se  porte  en  avant." 

Berard,  "  Cours  de  physiologie,"  Paris,  1851,  tome  iii., 
p.  603,  speaking  of  the  systole,  says: 

"  Le  sommet  des  ventricules  se  rapproche  de  la  base,  et  la  base 
du  sommet ;  il  suit  de  la  que  le  coeur  se  raccourcit." 

M.  H.  Milne  Edwards,  in  his  "  Leqons  sur  la  physiol- 
ogie et  I'anatomie  comparee  de  I'homme  et  des  animaux," 
tome  iv.,  p.  19,  now  in  course  of  publication,  in  speaking 
of  the  systole  of  the  heart,  says: 

"En  effet,  il  devient  presque  circulaire  a  sa  base;  la  portion 
voisine  de  la  region  ventriculaire  se  bombe  d'une  maniere  assez 
reguliere,  et  la  portion  inferieure  qui  avoisine  la  pointe  retrecit  et 
se  raccourcit." 

Finally,  in  the  "  Traite  de  physiologie  consideree  com- 
me  science  d'observation,"  par  C.  F.  Burdach,  Professor  a 
rUniversite  de  Konigsberg,  translated  into  French  by  Jour- 
dan,  are  to  be  found  the  opinions  of  the  German  physi- 
ologists; for  Burdach  w'as  assisted  in  the  preparation  of  this 


68    ACTION    OF    THE    HEART    AND    RESPIRATION 

work  by  Baer,  Mayen,  Meyer,  J.  Miillcr,  Rathke,  Valentin, 
and  Wagner:  tome  vi.,  p.  234,  he  says: 

"  La  contraction,  ou  systole,  s'opere  avec  la  rapidite  de  I'eclair. 
Le  coeur  se  reserre  sur  lui-meme ;  il  devicnt  plus  forme  et  plus  dur ; 
il  se  raccourcit,  c'est  a-dire  que  sa  base  et  son  sommet  se  recourbe 
un  peu." 

It  is  thus  seen  what  a  weight  of  authority  there  is  in 
favor  of  the  shortening  of  the  heart  during  the  systole, 
all  of  the  English,  French  and  German  authors  holding 
this  opinion,  and  all  of  them  denying  the  description  of 
Harvey,  who  states  that  the  heart  elongates  during  con- 
traction; "  that  it  is  everywhere  contracted,  but  more  espe- 
cially towards  the  sides,  so  that  it  looks  narrower,  relatively 
longer,  more  drawn  together."  *  It  is  only  in  this  country 
that  this  opinion  has  been  controverted;  and  though  ex- 
periments have  been  made  in  England,  with  reference  to 
this  point, f  they  confirmed  the  prevalent  view,  and  Amer- 
ican experiments  thus  far  have  stood  alone. 

In  November,  1839,  Drs.  Pennock  and  Moore  made  a 
number  of  experiments  upon  the  hearts  of  rams  and  young 
calves,  in  order  to  settle  disputed  points  in  the  change  of 
the  form  of  the  heart  during  its  action,  and  the  mechanism 
of  the  production  of  the  heart  sounds.  These  were  pub- 
lished in  the  "  Philadelphia  Medical  Examiner,"  No.  44, 
and  also  in  the  American  edition  of  "  Hope  on  the  Heart," 
1846.  page  59.  It  is  not  my  object  minutely  to  detail  these 
experiments;  I  shall  simply  state  that  the  animals  oper- 
ated on  were  stunned  by  a  blow  on  the  head,  a  bellows  was 
introduced  into  the  trachea,  by  means  of  which  artificial 
respiration  was  kept  up,  the  chest  was  opened  and  the 
movements  of  the  heart  were  observed.  With  reference 
to  the  form  and  length  of  the  heart  during  its  systole,  in  all 
of  these  experiments,  Drs.  Pennock  and  Moore  found  that 
the  heart  elongated.  Its  elongation  was  measured  with 
an  ordinary  shoemaker's  rule  and  found  in  one  experiment 
on  a  ewe  one  year  old,  to  be  one-quarter  of  an  inch. 

There  are  many  sources  of  dif^ficulty  in  examining  a 
phenomenon  apparently  so  simple  as  that  of  elongation 

*  Harvey's  Works,  published  by  the  Sydenham  Society,  page  21. 

f  Experiments  on  the  Motions  and  Sounds  of  the  Heart,  by  the  London 
Committee  of  the  British  Association  for  i838-'39  and  l839-'40.  Experiments 
for  1839-40.     "  Hope  on  the  Heart,"  Amer.  ed.,  1846,  p.  65. 


ACTION    OF   THE    HEART    AND    RESPIRATION    69 

or  shortening  during  the  systole  of  the  heart.  In  the  first 
place,  in  the  warm-blooded  animals,  as  the  dog,  the  heart's 
action  is  so  rapid  that  it  is  difficult  at  first  to  determine, 
even,  which  is  the  systole  and  which  is  the  diastole.  Then 
in  examining  the  heart,  when  the  lungs  are  being  alter- 
nately filled  and  emptied,  partly  covering  the  organ  at  each 
expansion,  its  apex  only  is  seen,  and  it  seems  to  retract 
when  the  heart  contracts.  In  order  to  demonstrate  the 
period  of  contraction  in  systole  of  the  ventricles,  I  have 
employed  the  proceeding  of  Harvey,  pushing  a  small  sil- 
ver tube  through  the  walls  of  the  heart  into  the  left  ven- 
tricle, withdrawing  the  stylet;  and  at  each  systole,  a  small 
jet  of  blood  is  forced  through  the  tube,  which  enables  one 
to  determine  at  a  glance  when  it  takes  place.  In  order  to 
determine  the  period  of  elongation  and  shortening  of  the 
heart,  I  have  devised  an  apparatus  by  means  of  which  this 
phenomenon  is  exaggerated.* 

In  reasoning  from  the  action  of  the  heart  in  the  lower 
animals  to  the  corresponding  movements  in  man,  one  should 
take  into  consideration  the  similarity  in  structure  and  ar- 
rangement of  the  organ  and  also  take  care  that  the  ordi- 
nary conditions  of  life  should  approximate  as  nearly  as 
possible  to  those  in  the  human  subject.  For  this  reason, 
the  most  valuable  experiments  are  on  the  warm-blooded 
animals;  and  the  phenomena  found  here  are  not  always 
verified  in  animals  lower  in  the  scale.  I  have  not  touched 
upon  the  change  in  form  of  the  heart  in  the  cold-blooded 
animals  in  the  body  of  this  paper;  for  although  such  inves- 
tigations are  interesting  in  themselves,  they  do  not  teach 
much  in  regard  to  human  physiology.  I  may  here  state, 
however,  that  in  the  turtle  the  heart  shortens  during  sys- 
tole. This  is  due  to  the  thinness  of  the  ventricle  and  the 
great  size  of  its  cavity  compared  with  the  warm-blooded 
animals.  The  heart  of  the  frog,  also,  shortens  slightly  dur- 
ing systole,  and  I  have  been  able  to  measure  the  actual 
extent  of  shortening  with  a  pair  of  ordinary  dividers.  An 
American  observer  f  has  described  an  experiment,  which 

*  Since  the  publication  of  this  article  in  1861,  I  have  become  convinced,  by 
a  number  of  more  exact  observations  on  the  exposed  heart,  that  the  ventricles 
shorten  during  their  systole.  I  have  therefore  omitted  the  wood-cut  and  de- 
scription of  the  apparatus  which  I  devised  and  which  seemed  to  show  elonga- 
tion of  the  ventricles. 

t  Dalton's  "  Treatise  on  Human  Physiology,"  2d  edition,  p.  258. 


70    ACTION    OF    THE    HEART    AND    RESPIRATION 

I  have  often  repeated,  to  prove  the  elongation  of  the  frog's 
heart  dnring  contraction,  which  consists  in  holding  the 
heart  by  the  base  between  the  thumb  and  finger,  with  the 
apex  upward,  and  irritating  it  with  the  point  of  a  needle. 
At  each  irritation  the  apex  is  elevated,  giving  an  appear- 
ance of  elongation.  This  appearance  is  not  deceptive;  the 
heart  actually  elongates,  but  the  position  in  which  it  is 
held,  the  ventricle  being  empty,  causes  its  flaccid  walls  dur- 
ing relaxation  to  collapse,  shortening  the  heart  more  than 
is  natural.  The  same  experiment  I  have  repeated  with 
the  heart  of  the  turtle;  but  in  altering  the  position  of  the 
heart  and  allowing  the  apex  to  hang  downward,  the  heart 
wall  be  found  to  shorten  during  the  systole,  the  dependent 
apex  being  drawn  up  by  the  muscular  contraction.  These 
experiments  prove  nothing  one  way  or  the  other.  It  is 
better,  in  all  experiments  of  this  description,  to  observe 
the  heart  in  situ,  while  its  cavities  are  filled  with  blood.  In 
observations  upon  the  irritability  and  various  properties 
of  the  anatomical  elements  of  the  heart,  phenomena  in 
cold-blooded  animals  may  be  studied  with  advantage;  for 
here  the  properties  are  the  same,  modified  only  by  the  vital 
condition  of  the  animal,  which,  by  diminishing  the  intensity 
of  their  manifestations,  render  their  study  more  simple. 

The  following  experiments  were  made  in  regard  to  the 
change  in  the  length  of  the  heart  during  the  systole  or 
contraction: 

Experiment  I.  January  28,  1861. — A  good-sized  dog  was  poi- 
soned with  curara,  artificial  respiration  was  kept  up,  and  the  heart, 
which  was  beating  strongly  and  naturally,  was  exposed  in  the  usual 
way.  Upon  holding  the  base  of  the  heart  between  the  index  and 
middle  fingers,  the  thumb,  placed  upon  the  apex,  was  sensibly  raised 
at  each  systole,  which  was  marked  by  the  hardening  of  the  ventri- 
cles. The  mekeoscope  *  was  now  applied  and  indicated  elongation 
with  every  systole,  or  contraction  of  the  ventricles.  The  systole 
of  the  heart  was  also  marked  by  slight  corrugation  of  the  surface 
of  the  ventricles,  by  a  tilting  movement  of  the  apex  upwards  and 
from  left  to  right  and  by  a  twisting  movement  of  the  heart  on  its 
axis,  from  left  to  right. 

Experiment  II.  February  i,  1861. — A  medium-sized  dog  was 
etherized  and  the  heart  exposed  in  the  usual  way.  The  facts  which 
are  recorded  in  Experiment  I  were  demonstrated  upon  this  animal. 
The  mekeoscope  was  applied  to  the  heart,  which  was  acting  nor- 

*  The  instrument  designed  to  show  elongation  of  the  ventricles,  the  descrip- 
tion of  which  has  been  omitted. 


ACTION    OF    THE    HEART    AND    RESPIRATION    71 

mally,  and  indicated  elongation  during  the  systole.  This  point  was 
verified  by  several  medical  gentlemen.  The  upper  extremity  of  the 
indicator  moved  one-half  an  inch  to  an  inch  with  every  beat  of 
the  heart.  It  was  determined  that  the  heart  elongated  during  the 
systole,  by  introducing  a  small  silver  canula  into  the  left  ventricle 
and  noticing  that  the  indicator  showed  elongation  every  time  a  jet 
of  blood  was  forced  through  the  canula. 

Experiment  III.  February  8,  1861. — A  large  dog  was  poisoned 
with  curara  and  the  heart  exposed  in  the  usual  way.  The  heart  was 
pulsating  well ;  the  mekeoscope  was  applied,  and  elongation  during 
the  systole  was  demonstrated.  The  various  points  recorded  in  Ex- 
periment I  were  confirmed  in  this  animal. 

Experiment  IV.  February  15,  1861. — A  medium-sized  dog 
was  etherized  and  the  heart  exposed  in  the  usual  way.  The  mekeo- 
scope was  applied  and  the  points  recorded  in  the  preceding  experi- 
ments were  confirmed. 

Experiment  V.  February  19,  1861. — A  good-sized  dog  was 
etherized  and  heart  exposed  in  the  usual  way.  The  points  recorded 
in  the  preceding  experiments  were  confirmed  in  this. 

Conclusions. — From  the  five  observations  here  re- 
ported, which  I  have  repeatedly  confirmed  in  unrecorded 
experiments,  there  is  one  legitimate  conclusion;  viz.,  that 
the  heart  of  the  dog  elongates  during  the  systole,  or  con- 
traction of  the  ventricles.  In  reasoning  from  the  inferior 
animals  to  the  human  subject,  taking  into  consideration  the 
anatomical  characters,  it  is  found  that  the  heart  in  the  dog 
has  essentially  the  same  anatomy  as  in  man;  but  instances 
are  on  record  where  the  heart  has  been  exposed  to  observa- 
tion in  the  human  subject.  Harvey  states,  in  his  report  of 
the  remarkable  case  of  the  son  ofthe  Viscount  Montgomery: 

"  We  also  particularly  observed  the  movements  of  the  heart, 
viz.,  that  in  the  diastole  it  was  retracted  and  withdrawn,  while  in 
the  systole  it  emerged  and  protruded ;  and  the  systole  of  the  heart 
took  place  at  the  moment  the  diastolic  impulse  in  the  wrist  was 
perceived :  to  conclude,  the  heart  struck  the  walls  of  the  chest,  and 
became  prominent  at  the  time  it  bounded  upwards  and  underwent 
contraction  of  itself."  * 

Haller  states  that  in  the  case  of  ectopia  cordis  which 
he  had  an  opportunity  of  observing,  the  heart  shortened 
during  its  systole,  as  it  did  in  animals  that  he  examined. 
Both  of  these  physiologists  had  the  opportunity  of  exam- 
ining the  action  of  the  heart  in  the  human  subject,  and 
both  verified  their  previous  observations  on  animals,  al- 
though the  results  were  contradictory. 

*  Harvey's  Works,  published  by  the  Sydenham  Society,  page  384. 


72    ACTION    OF   THE    HEART   AND   RESPIRATION 

It  seems,  then,  a  legitimate  conclusion  that  in  man,  as  in 
the  animals  examined,  the  heart  elongates  during  its  systole. 

Having  come  to  this  conclusion  from  actual  observa- 
tion, the  next  step  is  to  endeavour  to  account  for  it  by 
the  anatomical  arrangement  of  the  muscular  fibres  of  the 
heart.  This  can  easily  be  done;  for  if  a  heart  is  boiled  so 
as  to  dissolve  the  areolar  tissue  which  holds  together  its 
muscular  bundles,  the  fibres  can  easily  be  separated  and 
traced.  On  the  outside  is  a  layer  of  fibres,  common  to  both 
ventricles,  taking  a  spiral  course  from  left  to  right,  from 
the  base  to  the  apex.  Removing  these  superficial  fibres, 
beneath  them  is  found  a  mass  of  circular  fibres,  enveloping 
separately  the  right  and  left  ventricles.  The  action  of  these 
circular  fibres  in  shortening  is,  of  course,  to  increase  in 
diameter;  and  this  increase  in  diameter,  from  the  arrange- 
ment of  the  fibres,  would  produce  elongation  of  the  body 
of  the  heart. 

The  powerful  action  of  these  deep  circular  fibres  of  the 
heart  is  also  shown  by  a  phenomenon  noticed  during  con- 
traction; namely,  the  production  of  rugae  on  the  surface 
of  the  ventricles.  This  appearance  is  not  mentioned  by 
Harvey  but  is  noticed  by  Haller  in  the  work  I  have  before 
quoted,  vol.  i.,  page  389. 

"  Quando  cor  quietum,  aut  relaxatum,  a  stimulo  quocunque  in 
motem  cietur,  tunc  apparent  in  externa  cullis  superficiae  rugae,  in 
quas  fibrae  contractae  crispantur,  undulatae,  in  rana  et  anguilla  evi- 
dentur  transversae,  neque  in  cane,  fele,  aut  aliis  calidi  sanguinis 
animalibus  obscurae." 

This  may  be  because  the  superficial  fibres,  being  ex- 
posed to  the  air,  are  more  irregularly  and  less  powerfully 
contracted  than  the  deep,  or  it  may  be  a  phenomenon 
which  always  takes  place.  At  all  events,  it  indicates  that 
the  powerful  contraction  of  the  deep  circular  fibres  throws 
the  superficial  fibres  into  slight  longitudinal  folds  from  the 
greater  efBciency  of  their  action;  and  that  the  superficial 
fibres,  which  from  their  arrangement  might  tend  to  short- 
en the  heart,  do  not  compress,  in  their  contraction,  the 
deep  fibres,  but  that  the  latter  are  the  more  powerful  agents 
in  the  systole.  Thus  what  is  demonstrated  by  observation 
of  the  action  of  the  heart  in  the  living  animal  may  easily 
be  accounted  for  by  the  anatomical  arrangement  of  its 
muscular  fibres. 


ACTION    OF   THE    HEART    AND    RESPIRATION     73 

In  regard  to  the  hypothesis  of  Bassuel,  which  is  so 
often  quoted,  that  elongation  of  the  heart,  by  putting  the 
chordae  tendineae  on  the  stretch,  would  prevent  the  closure 
of  the  auriculo-ventricular  valves  and  therefore  is  impos- 
sible, I  have  nothing  to  say.  It  seems  to  me  sufficient  to 
have  demonstrated  on  the  living  animal  the  elongation; 
and  I  have  this  simple  fact  to  oppose  to  any  hypothet- 
ical objection. 

Cause  of  the  Rhythmical  Contractions  of  the 
Heart. — The  cause  of  the  regular  and  intermittent  con- 
tractions of  the  heart  is  obscure;  and  the  experiments  that 
I  have  made  on  this  subject,  though  far  from  being  so  satis- 
factory as  the  preceding,  still,  I  conceive,  define  the  extent 
of  actual  knowledge  and  bring  to  light  some  laws  which 
regulate  the  action  of  this  organ.  It  was  first  supposed 
that  the  blood  circulating  through  the  heart  was  the  cause 
of  its  rhythmical  contractions;  but  the  heart  will  continue 
to  beat  regularly  after  it  has  been  emptied  of  blood  and 
has  been  removed,  indeed,  from  the  body.  The  atmosphere 
was  then  supposed  to  supply  the  place  of  the  blood  as  a 
stimulus;  but  the  heart  of  a  frog  has  been  placed  under  the 
receiver  of  an  air-pump  and  still  it  continued  to  pulsate. 
Without  going  farther  into  the  opinions  now  entertained 
by  physiological  writers,  it  is  sufficient  to  state  that  physi- 
ologists are  not  yet  fully  acquainted  with  the  real  cause  of 
the  rhythmical  contractions  of  the  heart;  and  the  follow- 
ing experiments  were  made  in  the  hope  of  throwing  some 
light  upon  this  obscure  subject. 

Experiment  VI.*  November  14,  i860. — An  alligator,  six  feet 
in  length,  was  poisoned  with  curara,  the  thoracic  cavity  opened 
and  the  heart  exposed.  Some  experiments  were  then  made  upon 
this  organ  which  will  be  detailed  in  another  place ;  but,  twenty-four 
hours  after  the  operation,  the  heart,  which  had  been  left  in  situ, 
was  found  beating  regularly  and  with  considerable  force. 

Experiment  VII.  January  28,  1861. — An  alligator  of  the  same 
size  as  the  one  used  in  Experiment  VI.  was  poisoned  with  curara, 
the  chest  opened  and  observations  made  upon  the  heart.  The  heart 
was  left  in  situ  and  twenty-four  hours  after  death  was  found  pul- 
sating vigorously  and  regularly.  The  auricles  were  then  stimulated 
with  an  ordinary  magneto-electric  apparatus  during  the  intervals 
between  the  movements  of  the  organ ;  they  immediately  contracted, 
and  their  contraction  was  immediately  followed  by  contraction  of 

*  For  the  anatomy  of  the  heart  of  the  alligator,  see  Appendix. 


74    ACTION    OF    THE    HEART    AND    RESPIRATION 

the  ventricles.  Upon  applying  the  stimulus  to  the  ventricles  they 
contracted,  contraction  of  the  auricles  following  immediately. 
These  phenomena  were  repeatedly  verified  in  the  presence  of  two 
assistants ;  the  same  results  followed  irritation  with  the  point  of  a 
scalpel.  The  heart  was  then  removed  from  the  body  and  emptied 
of  ijlood.  When  placed  upon  the  table  it  pulsated  quite  rapidly 
(about  ten  times  i)er  minute  instead  of  four  or  five)  but  its  con- 
tractions were  feeble.  On  stimulating  the  ventricles,  they  con- 
tracted powerfully,  feeble  contractions  of  the  auricles  following. 
On  stimulating  the  auricles,  they  generally  contracted  feebly  and 
sometimes  no  movement  was  excited;  but  the  ventricles  contracted 
invariably. 

The  aortic  (there  are  two  in  the  alligator)  were  then  tied  and 
the  heart  was  filled  with  blood  (which  was  prevented  from  coagu- 
lating by  the  addition  of  a  little  solution  of  carbonate  of  soda)  by 
injecting  it  through  the  right  auricle  and  confining  it  with  a  liga- 
ture. The  heart  then  began  to  contract  regularly  and  forcibly.  The 
auricles  contracted  first,  and  then  the  ventricles,  making  about  four 
pulsations  per  minute.  The  contractions  were  powerful  and  regu- 
lar, contrasting  strongly  with  the  rapid  and  feeble  action  before 
the  organ  had  been  filled  with  blood.  The  heart  was  evidently 
over-distended,  but  was  relieved  by  dividing  the  coronary  artery, 
allowing  some  of  the  blood  to  escape,  until  it  was  reduced  to  about 
its  normal  condition  of  fullness.  Electric  stimulation  of  the  auri- 
cles excited  contraction,  followed  by  contraction  of  the  ventricles, 
and  the  same  stimulus  applied  to  the  ventricles  excited  contraction, 
followed  by  contraction  of  the  auricles,  in  about  the  same  manner 
as  when  these  experiments  were  made  upon  the  organ  before  its 
removal  from  the  body.  This,  also,  was  repeatedly  verified.  The 
heart  was  then  emptied  of  blood  and  placed  upon  a  clean  plate. 
The  contractions  became  such  as  were  noted  immediately  after  the 
heart  had  been  removed  from  the  animal  and  before  it  had  been 
filled  artificially  with  blood. 

The  heart  was  then  filled  v^^ith  water.  The  contractions  were 
not  so  powerful  and  regular  as  when  it  had  been  filled  with  blood, 
and  were  limited  chiefly  to  the  ventricles.  They  were  also  much 
more  rapid.  It  was  impossible  to  establish  the  contraction  of  the 
auricles  on  electric  stimulation,  followed  immediately  by  contrac- 
tion of  the  ventricles,  and  the  reverse,  as  when  the  heart  was  filled 
with  blood.  The  ventricles,  still  filled  with  w-ater  confined  in  their 
cavity,  were  then  firmly  grasped  in  the  hand  so  as  to  subject  the 
muscular  fibres  to  powerful  compression.  From  that  time  the  heart 
entirely  ceased  its  contractions  and  became  hard,  like  a  muscle  in 
a  state  of  cadaveric  rigidity.  The  experiment  was  then  terminated 
twenty-eight  hours  after  the  death  of  the  animal ;  and  the  heart 
was  still  beating  until  its  pulsations  were  arrested  in  the  manner 
described.* 

Experiment  VIII.     On  Turtles. — The  hearts  of  turtles  were 

*  These  observations  were  begun  twenty-four  hours  after  the  death  of  the 
animal. 


ACTION    OF    THE    HEART    AND    RESPIRATION    75 

exposed  and  removed  from  the  body  while  pulsating.  Electric 
stimulation  applied  to  the  auricles  produced  contraction,  followed 
by  contraction  of  the  ventricle ;  and  a  stimulus  applied  to  the  ven- 
tricle produced  a  contraction,  followed  by  contraction  of  the  auri- 
cles. This  took  place  whether  the  irritation  was  electric  or  me- 
chanical, like  the  point  of  a  needle,  and  indifferently  whether  the 
heart  was  removed  from  the  animal  or  left  in  situ. 

These  observations  were  repeatedly  verified  upon  the  same 
turtles  and  in  a  number  of  subsequent  experiments. 

Experiment  IX.  March  11,  1861. — The  heart  of  a  turtle  was 
removed  and  the  ventricles  separated  from  the  auricles.  The  auri- 
cles contracted  spontaneously  and  regularly  for  twenty  minutes,  the 
time  during  which  their  movements  were  observed ;  and  the  ven- 
tricle contracted  irregularly  and  at  intervals  of  two  minutes  or 
more.  The  ventricle  always  contracted  when  irritated  with  the 
point  of  a  needle. 

In  this  experiment  I  was  not  certain  that  the  ventricle  con- 
tracted without  the  application  of  a  stimulus,  for  it  was  exposed 
to  currents  of  air,  jars  of  the  table,  etc.,  which  might  be  capable 
of  producing  contractions. 

Experiment  X.  March  13,  1861. — The  heart  of  a  turtle  was 
removed  from  the  body  while  it  was  beating  regularly,  and  the 
ventricle  was  separated  from  the  auricles  as  in  the  preceding  ex- 
periment. Both  auricles  and  ventricle  were  then  placed  under  a  bell 
glass  and  carefully  observed  for  an  hour  and  thirty  minutes. 

When  placed  under  the  bell  glass,  the  auricles  contracted  regu- 
larly twelve  to  sixteen  times  per  minute.  No  contraction  of  the 
ventricle  occurred. 

Five  minutes  after. — Auricles  the  same  and  the  ventricle  con- 
tracted once. 

Seven  minutes  after. — Auricles  contracting  regularl}^  sixteen 
per  minute,  ventricle  contracted.  (The  apparatus  was  shifted  from 
one  table  to  another,  which  might  have  been  the  cause  of  the  ven- 
tricular contraction.) 

Ten  minutes. — Auricles  the  same  and  ventricle  contracted. 

Eleven  minutes. — Ventricle  contracted. 

Twelve  minutes. — Ventricle  contracting  regularly  five  times  in 
two  minutes. 

Twenty-two  minutes. — Ventricle  contracting  regularly  seven 
times  in  two  minutes ;  auricles  contracting  twenty-two  times  per 
minute. 

Thirty-two  minutes. — Ventricle  contracting  four  times  per 
minute;  contractions  of  auricles  rapid  but  irregular. 

Forty-two  minutes. — One  and  three-quarter  minutes  between 
the  contractions  of  the  ventricle. 

One  hour  and  thirty  minutes. — Auricles  contracting  eight  times 
per  minute ;  two  minutes  between  the  contractions  of  the  ventricle. 

Experiment  XI.  INIarch  13,  1861. — The  heart  of  a  turtle  was 
removed  and  placed  under  a  bell  glass. 

Thirty  minutes  after. — It  pulsated  twelve  times  per  minute, 
contraction  of  the  auricles  always  preceding  that  of  the  ventricle. 


76    ACTION   OF   THE    HEART    AND    RESPIRATION 

Sixty  minutes. — The  heart  pulsated  six  times  per  minute,  the 
auricles  contracting  first. 

In  making  these  experiments,  it  was  found  that  the  operation 
of  removing  and  dividing  the  heart  produced  a  shock  which  inter- 
fered at  first  with  its  action.  The  heart  recovered  from  it,  however, 
in  about  thirty  minutes. 

ExpERiiMENT  XII.  February  15,  1861. — A  medium-sized  dog 
was  etherized  and  his  heart  exposed  in  the  usual  way,  artificial 
respiration  being  kept  up.  While  respiration  w^is  being  actively 
performed  by  means  of  bellows  and  while  the  heart  was  pulsating 
vigorously,  the  organ  was  suddenly  removed  from  the  body  by  a 
single  sweep  of  the  knife.  It  was  immediately  placed  upon  the 
table  and  contracted  so  vigorously  that  it  bounded  up  at  every 
pulsation  like  an  India-rubber  ball.  This  remarkable  phenomenon 
lasted  for  a  few  seconds  only,  but  the  heart  pulsated  regularly  for 
two  minutes.  A  powerful  shock  was  then  passed  through  it  by 
means  of  a  magneto-electric  apparatus,  with  the  effect  of  imme- 
diately arresting  all  regular  pulsations ;  but  this  was  followed  by 
a  general,  irregular  vermicular  action  of  the  fibres.  This  continued 
for  thirty  minutes.  At  first  irregular  contractions  could  be  excited 
by  feeble  currents;  but  after  thirty  minutes  this  became  impossible. 
When  the  vermicular  action  of  the  muscular  fibres  had  ceased  no 
contraction  could  be  excited  by  electric  or  mechanical  stimulus. 

Experiment  XIII.  March  13,  1861. — A  turtle  was  poisoned 
with  a  variety  of  curara  which  arrests  or  depresses  the  action  of 
the  heart,  by  injecting  about  a  grain  of  it  in  solution  under  the  skin. 
In  thirty  minutes  the  animal  was  dead  and  the  exposed  heart  was 
found  beating  feebly  and  slowly.  On  applying  electricity  to  the 
exposed  muscles,  their  irritability  was  found,  by  actual  comparison 
with  the  exposed  muscles  of  turtles  which  had  not  been  poisoned,. 
to  be  very  much  diminished. 

Experiment  XIV.  March  13,  1861. — The  preceding  experi- 
ment was  repeated  upon  another  turtle.  When  all  signs  of  life  had 
disappeared,  the  heart  was  exposed  and  found  beating  feebly^ 
Muscular  irritability  was  much  diminished. 

It  will  be  seen  by  these  few  experiments  that  it  is  diffi- 
cult, if  not  impossible,  in  the  present  state  of  knowledge 
and  with  such  data  alone,  to  say  why  the  heart  contracts 
in  the  manner  which  is  characteristic  of  it.  If  the  cause 
resides  in  the  nervous  system,  it  must  be  in  nerve-centres 
existing  in  the  substance  of  the  organ.  In  short,  the  con- 
traction of  the  heart  is  dependent  either  upon  nerves  in 
its  substance  or  upon  an  inherent  property  peculiar  to  its 
muscular  fibres.  The  nervous  influence,  if  there  is  any,, 
must  come  from  the  sympathetic  or  organic  system,  be- 
cause an  organ  must  remain  connected  with  the  cerebro- 
spinal centres  in  order  that  any  influence  should  be  derived 
from  this  system. 


ACTION    OF   THE    HEART    AND    RESPIRATION    77 

Dr.  Robert  Lee,  of  London,  has  demonstrated  the  ex- 
istence of  sympathetic  ganglia  in  the  substance  of  the 
heart ;  but  it  is  impossible  to  say  positively  that  an  influence 
derived  from  these  is  the  cause  of  its  rhythmical  contrac- 
tions. The  most  that  can  be  said  on  this  subject  is  that 
the  muscular  fibres  of  the  heart  have  an  inherent  property 
of  contraction  so  long  as  they  are  in  a  state  of  physical  and 
chemical  integrity;  that  this  contraction,  like  that  of  all 
other  muscles,  is  followed  by  a  relaxation;  but  the  fibres  of 
the  heart,  after  the  short  period  of  repose  which  is  thus 
allowed  them,  contract  again.  I  know  that  in  this  state- 
ment I  am  simply  describing  the  phenomena  of  the  heart's 
action  and  confessing  ignorance  as  to  its  cause;  but  we  are 
in  the  best  position  to  acquire  information  upon  any  sub- 
ject when  admitting  the  real  state  of  knowledge,  and  not 
attempting  to  explain  what,  with  our  resources,  is  incapable 
of  explanation. 

I  have  given  the  sum  of  actual  knowledge  of  the  cause 
of  the  heart's  action  as  an  introduction  to  a  study  of  some 
of  the  properties  of  the  muscular  fibres  of  this  organ  and 
the  laws  by  which  their  contractions  are  regulated. 

L  The  muscular  fibres  of  the  heart  possess  in  a  remark- 
able degree  that  property  known  as  irritability.  This  is 
more  marked  in  the  auricles  than  in  the  ventricles.  The 
auricles  contract  readily  upon  the  application  of  a  stimulus 
applied  to  the  surface;  and  Virchow  has  demonstrated  that 
the  internal  surface  is  much  more  irritable  than  the  ex- 
terior. 

IL  It  has  been  shown  by  experiments  made  by  Erich- 
sen  *  that  the  action  of  the  heart  is  arrested  in  about  thirty 
minutes,  in  the  warm-blooded  animals,  by  ligature  of  the 
coronary  arteries,  artificial  respiration  being  continued, 
showing  that  the  presence  of  a  certain  quantity  of  blood 
in  the  substance  of  the  organ  is  necessary  to  the  irrita- 
bility of  its  muscular  fibres. 

in.  Experiments  here  detailed,  as  well  as  those  of  other 

*  These  experiments  were  made  by  pithing  the  animal,  keeping  up  artificial 
respiration  and  opening  the  chest.  It  was  found  that  the  heart  continued  to 
beat  under  these  conditions,  for  one  to  two  hours,  but  was  arrested  in  a  short 
time  if  the  coronary  arteries  were  ligated.  The  mean  of  six  experiments  showed 
the  duration  of  the  heart's  action,  after  ligation  of  these  vessels,  to  be  23^ 
minutes.  The  experiments  are  to  be  found  in  the  "  Medical  Gazette,"  July 
S,  1842. 


78    ACTION    OF   THE    HEART    AND    RESPIRATION 

observers,  show  that  the  heart  of  cold-blooded  animals, 
especially  the  alligator,  retains  its  irritability  for  a  long- 
time after  death.  In  Experiment  VII.  the  heart  was  beat- 
ing  twenty-eight  hours  after  death,  when  its  action  was 
artificially  arrested.  This  was  due  in  part  to  the  action 
of  curara;  for  Bernard  has  lately  shown  that  muscular  irri- 
tability remains  in  frogs  poisoned  with  this  agent  much 
longer  than  ordinary,  and  that  the  action  of  the  heart  is 
also  prolonged.*  This  property  renders  curara  valuable 
in  studying  the  movements  of  the  heart. 

IV.  The  same  experiments  (on  turtles  and  alligators) 
show  that  a  stimulus,  mechanical  or  electric,  applied  to 
one  part  of  the  heart  is  propagated  to  the  other,  and  also 
tend  to  show  that  the  stimulus  which,  in  the  natural  action 
of  the  organ,  excites  the  auricles  to  contraction,  is  propa- 
gated from  them  to  the  ventricles.  These  experiments  are 
not  new.  The  same  fact  has  been  noticed  by  Mr.  Paget 
in  the  heart  of  the  turtle  and  was  published  in  the  "  British 
and  Foreign  Medico-Chirurgical  Review,"  vol.  xxi.,  p.  550. 

V.  Experiments  IX.  and  X.  show  that  the  irritability 
of  the  auricles  and  ventricles  are  separate  and  distinct;  that 
the  auricles  possess  this  irritability  in  a  much  greater  de- 
gree than  the  ventricles,  as  demonstrated  by  the  distinct 
contractions  of  auricles  and  ventricles  when  separated 
from  each  other  and  the  much  greater  frequency  of  con- 
tractions of  the  auricles;  that  the  contraction  of  the  auri- 
cles acts  as  a  stimulus  to  the  ventricles,  for  when  they  are 
left  together,  as  in  Experiment  XL,  and  the  heart  is  re- 
moved from  the  body,  the  auricles  always  contract  first, 
and  their  contraction  is  invariably  followed  by  contraction 
of  the  ventricles. 

VI.  Experiment  VII.  shows  that  the  heart  of  the  alli- 
gator, if  emptied  of  blood,  does  not  contract  regularly; 
but  that  its  regular  contractions  return  if  the  blood  is  in- 
jected into  and  confined  in  its  cavities;  also  that  the  propa- 
gation of  a  stimulus  from  auricles  to  ventricles  is  not  inva- 
riable in  the  heart  emptied  of  blood,  but  that  it  may  always 
be  demonstrated  in  the  heart  filled  with  blood  either  natu- 
rally or  artificially. 

VII.  The  same  experiment  shows  that  the  heart  filled 

*  Bernard,  "  Substances  toxiques  et  medicamen tenses,"  page  320  ef  seq. 


ACTION    OF   THE    HEART    AND    RESPIRATION    79 

with  water  does  not  act  normally  after  removal  from  the 
body,  as  it  does  if  blood  is  injected  into  its  cavities,  but 
more  rapidly  and  less  ef^ciently;  and  finally,  that  powerful 
compression  seems  to  paralyze  the  muscular  fibres  instant- 
ly and  cause  them  to  take  on  cadaveric  rigidity. 

VIII.  Experiment  XII.  shows  that  a  powerful  electric 
shock  passed  through  the  substance  of  the  heart,  in  warm- 
blooded animals,  immediately  arrests  its  regular  pulsa- 
tions. 

IX.  Agents  which  abolish  or  diminish  general  muscular 
irritability,  like  the  sulphocyanide  of  potassium,  have  a  cor- 
responding effect  upon  the  heart.  This  is  a  fact  now  well 
established. 

Experiments  XIII.  and  XIV.  show  that  a  certain  kind 
of  curara,  which  arrests  the  action  of  the  heart,  diminishes 
very  much  the  general  muscular  irritability. 

Conclusions. — From  the  facts  stated  above,  the  fol- 
lowing deductions  can  legitimately  be  made: 

The  natural  stimulus  of  the  regular  movements  of  the 
heart  is  the  blood;  and  this  stimulus  can  not  be  adequately 
supplied  by  any  other  fluid  of  less  density,  like  w^ater; 
so  that,  in  conditions  in  which  the  blood  becomes  watery, 
as  in  the  reaction  after  copious  bleeding  or  in  an?emia,  the 
contractions  of  the  heart  are  feeble  and  rapid;  and  in  affec- 
tions in  which  the  blood  becomes  denser  than  in  health, 
as  in  plethora,  the  heart  contracts  more  slowly  and  with 
abnormal  force. 

In  the  normal  action  of  the  heart,  this  stimulus  first 
affects  the  auricles,  which  are  first  distended  with  blood, 
and  is  propagated  thence  to  the  ventricles. 

All  irritability  of  the  muscular  fibres  of  the  heart  may 
be  immediately  arrested  by  forcible  compression;  and  its 
property  of  regular  contraction  may  be  abolished  by  a 
powerful  electric  current. 

A  peculiarity  of  the  muscular  irritability  of  the  heart  is 
that  when  the  organ  has  ceased  to  contract  spontaneously 
while  in  the  chest  or  after  removal  from  the  body,  contrac- 
tions can  not  be  excited  by  ordinary  stimuli,  such  as  irri- 
tation with  the  point  of  a  needle  or  scalpel  or  electricity; 
while  such  irritation  applied  to  any  of  the  muscles  will  pro- 
duce contractions.     In  an  experiment  which  I  made  on 


So    ACTION    OF    THE    HEART    AND    RESPIRATION 

this  point  upon  the  heart  of  a  dog,  I  found  that  the  heart 
ceased  beating-  in  about  ten  minutes  after  the  stoppage  of 
respiration  (the  dog  had  been  etherized  and  his  heart  ex- 
posed), and  that  after  that  time  electric  stimulation  ap- 
plied to  the  heart  failed  to  produce  contraction,  although 
the  sterno-mastoid  and  muscles  of  the  chest,  which  had 
been  exposed  during  the  operation,  contracted  powerfully 
on  the  application  of  the  stimulus.  This  favors  the  idea 
that  the  muscles  of  the  heart  differ  from  the  other  striped 
muscles  in  possessing  the  inherent  property  of  regular 
contraction;  for  they  continue  to  contract  till  they  have 
lost  their  irritability,  and  then  can  not  be  excited  to  action 
artificially.  This  is  true  only  when  the  heart  is  allowed 
to  stop  spontaneously  and  the  duration  of  its  pulsations 
is  not  interfered  with  by  placing  it  in  a  vacuum  (which, 
while  it  does  not  arrest,  abridges  the  duration  of  the  heart's 
action)  or  by  other  means.* 

The  irritability,  which  in  ordinary  muscles  is  manifested 
by  their  contraction  upon  the  application  of  a  stimulus, 
and,  in  the  case  of  the  heart,  by  regular  pulsations  so  long 
as  the  fibres  retain  their  integrity,  is  really  identical  in  the 
heart  and  general  muscular  system;  it  is  greatest  in  the 
heart  and  is  much  greater  in  the  auricles  than  in  the  ven- 
tricles, as  shown  by  experiments.  In  the  heart  this  irrita- 
bility becomes  extinct  before  general  muscular  irritability 
is  lost,  for  the  regular  contractions  of  the  organ  after  death 
or  after  removal  from  the  body  wear  it  out,  while  the  gen- 
eral muscular  system,  if  unstimulated,  is  in  a  state  of  re- 
pose. It  is  also  true  that  muscular,  like  nervous  irritabil- 
ity, disappears  soonest  in  parts  where  it  is  most  intense, 
as  it  does  in  animals  like  the  warm-blooded,  the  functions 
of  which  are  most  active.  The  ventricles  seem  to  depend 
for  their  stimulus  upon  the  contraction  of  the  auricles;  for 
when  separated,  as  in  Experiment  X.,  the  ventricles  do  not 
contract  so  frequently  as  the  auricles,  or  so  frequently  as 
when  their  connection  with  them  is  not  severed.    The  ven- 

*  I  have  not  made  a  sufficient  number  of  experiments  to  be  able  to  state 
this  positively,  but  it  is  certain  that  the  general  muscular  irritability  continues 
long  after  the  heart  has  ceased  to  beat  ;  and  the  question  arises,  in  studying  the 
heart  of  a  cold-blooded  animal  in  a  quiescent  state,  but  contracting  upon  irrita- 
tion, whether  it  does  not  contract  spontaneously  but  at  remote  intervals,  as  in 
Experiment  X.  This  question  can  be  answered  only  by  more  extended  obser- 
vations. 


ACTION    OF    THE    HEART   AND    RESPIRATION    8i 

tricles  possess,  then,  an  independent  irritability  which  is 
much  less  than  that  of  the  auricles. 

The  irritability  of  the  heart  is  like  the  general  muscular 
irritability  in  another  respect.  Most  agents  which  para- 
lyze the  muscular  system  paralyze  the  heart;  and  Experi- 
ments XIII.  and  XIV.  show  that  the  peculiar  variety  of 
curara,  which  acts  upon  the  heart,  diminishes  to  a  great 
extent  the  irritability  of  the  general  muscular  system.  On 
the  contrary,  the  most  common  variety  of  curara,  which 
paralyzes  the  motor  nerves  and  the  sympathetic  system, 
leaves  the  muscular  irritability  intact,  and  also  the  move- 
ments of  the  heart,  which  will  continue  for  a  long  time  after 
death,  if  respiration  is  artificially  performed. 

Mechanical  Causes  which  arrest  the  Heart's 
Action. — In  asphyxia  and  in  some  organic  diseases  of  the 
heart,  there  is  arrest  of  the  action  of  this  organ.  When 
this  is  caused  by  mechanical  obstruction,  as  in  disease  at 
the  aortic  orifice,  death  is  attributed  to  overdistension  of 
the  heart;  but  in  asphyxia  it  becomes  a  question  whether 
death  is  due  to  this  cause  or  to  the  circulation  of  venous 
blood  in  its  substance,  as  was  supposed  by  Bichat.  In 
experiments  on  the  lower  animals,  when  we  expose  the 
heart  and  keep  up  artificial  respiration,  we  can  easily  see 
the  immediate  effects  of  arrest  of  respiration  upon  its 
action.  It  becomes  distended,  changes  from  a  red  to  a  blue 
color,  showing  that  venous  blood  is  circulating  in  its  sub- 
stance, and  gradually  its  movements  cease.  But  if  respi- 
ration is  recommenced  before  its  action  has  been  entirely 
arrested,  it  immediately  becomes  florid,  its  distension  is 
gradually  relieved  and  soon  its  normal  action  is  reestab- 
hshed.  In  order  to  determine  the  cause  of  stoppage  of 
the  heart  in  asphyxia,  I  made  the  following  experiments. 

Experiment  XV.  February  i,  1861. — A  dog  was  etherized 
at  2.15  p.  M.  and  the  chest  opened  in  the  usual  way.  At  2.25  I 
stopped  respiration.  In  fifty  seconds  the  heart  became  dark  and 
much  distended.  Respiration  was  recommenced,  which  had  the 
effect  of  soon  restoring  normal  action.  The  pulmonary  artery  and 
aorta  were  then  tied  suddenly  with  a  strong  cord.  The  heart  be- 
came much  distended,  was  of  a  red  color,  labored  more  than  when 
respiration  had  been  stopped,  and  in  forty  seconds  it  became  neces- 
sary to  remove  the  ligature  for  fear  of  permanently  arresting  its 
action.  After  removing  the  ligature,  the  heart  gradually  returned 
6 


82    ACTION    OF   THE    HEART    AND    RESPIRATION 

to  its  normal  condition,  but  more  slowly  than  when  respiration  had 
been  arrested  for  fifty  seconds. 

At  2.40  a  grain  of  curara  was  injected  into  the  areolar  tissue. 
At  4.10  the  aorta  was  compressed.  The  heart  labored,  and  in  twen- 
ty-five seconds  the  compression  was  removed  and  it  gradually  re- 
sumed its  normal  action.  Respiration  was  then  suspended  with  the 
same  effect  on  the  heart.  In  one  minute  respiration  was  recom- 
menced and  the  heart  resumed  its  normal  action. 

In  this  experiment  compression  of  the  aorta  and  pul- 
monary artery  produced  more  trouble  in  the  heart's  action, 
the  trouble  came  on  more  rapidly,  and  it  was  longer  be- 
fore its  action  became  normal  than  when  respiration  was 
stopped;  though  when  the  vessels  were  compressed  the 
heart  was  florid,  showing  red  blood  circulating  in  its  sub- 
stance, and  when  respiration  was  arrested  it  became  dark. 

Experiment  XVI.  February  8,  1861. — A  large  dog  was  poi- 
soned with  curara  and  the  chest  opened  in  the  usual  way.  Respi- 
ration was  stopped  for  two  and  a  half  minutes.  The  heart  became 
very  dark,  much  distended,  and  labored ;  but  when  respiration  was 
recommenced  it  became  gradually  relieved,  and  in  a  few  minutes 
regained  its  normal  action.  The  aorta  was  then  tied  for  two  min- 
utes. The  heart  remained  red,  became  more  distended,  and  la- 
bored more  than  in  the  previous  instance,  but  gradually  resumed 
its  action  after  the  ligature  was  removed.  During  the  time  that 
the  aorta  was  compressed,  here,  as  in  Experiment  XV,  respiration 
was  continued. 

In  this  experiment  I  tried  to  ascertain  how  long  the 
heart  could  be  kept  distended  by  asphyxia  or  compression 
of  the  great  vessels  and  yet  resume  its  functions  when  the 
cause  of  the  distension  was  removed. 

Conclusions. — Great  distension  of  the  heart  will  pro- 
duce paralysis  of  its  muscular  fibres;  and  this  is  the  cause 
of  the  arrest  of  its  action  in  asphyxia  and  in  many  cases  of 
sudden  death,  not  the  circulation  of  venous  blood  in  its 
substance,  as  was  supposed  by  Bichat.  The  experiments 
which  I  have  detailed  demonstrate  this  fact  in  regard  to 
asphyxia;  for  here  it  is  shown  that  the  greater  the  dis- 
tension the  sooner  the  heart  ceases  its  contractions.  The 
heart  is  arrested  sooner  by  ligature  of  the  great  vessels, 
when  red  blood  circulates  in  its  substance,  than  by  arrest 
of  respiration,  when  it  is  supplied  with  black  blood,  because 
in  the  first  instance  the  distension  is  greater. 

The  mechanism  of  this  muscular  paralysis  is  the  same 


ACTION    OF    THE    HEART   AND    RESPIRATION    83 

as  that  of  the  paralysis  of  any  striped  muscle  by  straining. 
If  a  muscle  is  violently  extended,  as  in  a  dislocation,  there 
is  loss  of  function  for  a  period  proportionate  to  the  sever- 
ity of  the  strain.  The  same  is  true  in  regard  to  the  heart; 
but  the  constant  action  of  the  heart  is  necessary  to  exist- 
ence; and  when  this  muscle  is  paralyzed  by  straining  of  its 
fibres  by  distension,  the  animal  dies  before  it  has  time  to 
recover  its  functions.  In  case  of  asphyxia,  then,  so  long 
as  the  heart  continues  to  act,  though  feebly  and  at  long 
intervals,  artificial  respiration  will  probably  restore  Hfe; 
but  after  its  action  has  been  suspended  there  can  be  little 
or  no  hope  of  restoring  it. 

Cases  of  sudden  death  from  organic  disease  of  the  heart, 
contrary  to  the  popular  impression,  are  not  common;  and 
the  only  form  of  this  affection  in  which  sudden  death  is 
likely  to  occur  is  disease  at  the  aortic  orifice.  In  this  form 
of  the  affection,  the  heart  is  liable  to  overdistension  from 
any  cause  which  increases  the  force  and  rapidity  of  its  ac- 
tion; and  death  results  from  stoppage  of  the  heart,  in  the 
same  manner  as  when  the  aorta  has  been  tied,  as  was  done 
in  the  experiments  before  detailed. 

In  death  from  injury  to  the  head,  as  from  apoplexy, 
respiration  is  interfered  with  and  distension  of  the  heart 
occurs  in  precisely  the  same  way  as  when  artificial  respira- 
tion is  interrupted  in  experiments  on  the  lower  animals. 
This  is  further  illustrated  by  the  experiments  of  observers 
who  stun  the  animals  upon  which  they  operate  in  order  to 
observe  the  action  of  the  heart.  If  artificial  respiration  is 
not  immediately  established,  the  heart  ceases  to  act,  from 
distension,  and  the  animal  dies. 

In  death  from  poisoning  by  opium,  the  respiratory 
muscles  are  paralyzed  by  the  poison,  and  the  heart  ceases 
to  act  in  the  same  manner  as  in  asphyxia  from  any  cause. 
It  would  then  follow  that  if  artificial  respiration  is  kept  up 
until  the  power  of  the  poison  is  exhausted  and  natural  res- 
piration is  gradually  restored,  the  life  of  the  patient  would 
be  preserved;  and  the  well-known  experiments  of  Sir  Ben- 
jamin Brodie  with  opium  and  curara  have  proved  that  this 
is  the  fact. 

In  some  cases  of  convulsions,  when  death  occurs  res- 
piration is  interfered  with  and  the  heart  is  arrested  by  over- 
distension.   This  is  true  of  all  nervous  diseases  which,  from 


84    ACTION    OF    THE    HEART   AND    RESPIRATION 

their  action  upon  the  general  system  or  upon  the  respira- 
tory apparatus,  produce  death. 

In  death  from  introduction  of  air  into  the  veins,  the  air 
going  to  the  right  side  of  the  heart  is  divided  into  minute 
bubbles  which  can  not  pass  through  the  lungs.  The  heart 
becomes  distended  from  this  obstruction  and  ceases  to  con- 
tract from  overdistension. 

It  appears,  therefore,  that  distension  of  the  heart,  by 
its  mechanical  action  on  the  muscular  fibres,  may  cause 
stoppage  of  the  circulation  and  death;  that  sudden  death 
may  generally  be  attributed  to  this  cause;  that  the  cause 
of  this  distension  may  usually  Ije  referred  to  the  respiratory 
function;  and  that  the  indications  are,  therefore,  to  rees- 
tablish this  function,  by  artificial  respiration  or  otherwise, 
w'hen  it  is  arrested,  or  to  prevent  the  diseases  under  which 
the  patient  may  labor  from  interfering  with  it. 

Influence  of  the  Pneumogastric  Nerve  on  the 
Action  of  the  Heart. — The  heart,  like  other  of  the 
striped  muscles,  is  provided  with  nerves  derived  from  the 
cerebro-spinal  system;  but  the  action  of  the  nerves  which 
go  to  the  heart  differs  from  the  nervous  influence  exerted 
upon  any  other  muscle.  If  a  nerve  distributed  to  a  vol- 
untary muscle  is  divided  the  muscle  is  paralyzed;  but  after 
division  of  the  pneumogastric  nerve,  which  is  distributed 
in  part  to  the  heart,  this  organ,  far  from  being  paralyzed, 
is  accelerated  in  its  action.  Bernard  has  found  that  di- 
vision of  the  pneumogastrics  in  the  neck  increases  the 
number  of  cardiac  pulsations,  sometimes  even  doubHng 
them;  but  that  the  force  of  the  contractions  is  diminished. 
When  the  peripheral  end  of  a  divided  nerve  going  to  a 
muscle  is  faradized  the  muscle  is  thrown  into  violent  con- 
tractions; but  stimulation  of  the  peripheral  ends  of  the 
pneumogastrics  arrests  the  action  of  the  heart.  These  ob- 
servations were  made  in  1845,  by  Weber,  and  have  been 
repeatedly  verified  by  physiologists  since  that  time;  but  the 
cause  of  this  peculiarity  of  action  has  not  been  satisfacto- 
rily explained. 

In  the  first  place  it  is  important  to  determine  whether 
the  electric  stimulus  is  conveyed  to  the  heart  directly 
through  the  motor  filaments  of  the  pneumogastrics  or 
through  the  sensor}-  filaments  to  the  nerve-centres,  and 


ACTION    OF    THE    HEART    AND    RESPIRATION    85 

by  reflex  action  operates  through  other  nerves  on  the 
heart.  This  is  easily  ascertained  by  dividing  both  pneu- 
mogastrics  and  stimulating  alternately  the  central  and 
peripheral  ends;  when  it  is  found  that  the  current  applied 
to  the  peripheral  extremities  will  arrest  the  action  of  the 
heart,  while  the  same  stimulus  applied  to  the  central  ends 
produces  no  such  effect.  By  means  of  curara,  the  motor 
nerves  and  the  motor  filaments  of  the  mixed  nerves  are 
paralyzed,  the  two  systems  being  dissected  out,  as  it  were, 
by  this  curious  poison;  and  it  is  found  that  when  the  pneu- 
mogastric  nerves  are  stimulated  in  an  animal  poisoned  by 
this  agent,  it  is  impossible  to  arrest  the  action  of  the  heart. 
This  fact  was  pointed  out  by  Bernard  *  and  has  been  re- 
peatedly verified  by  myself. 

If  both  pneumogastric  nerves  of  a  dog  are  isolated  in 
the  middle  of  the  neck  and  subjected  to  a  feeble  current, 
the  first  effect  upon  the  movements  of  the  heart,  when  this 
organ  is  exposed  to  view,  is  a  diminution  in  the  frequency 
of  its  pulsations.  If  the  current  is  then  gradually  increased 
in  intensity,  the  action  of  the  heart  is  arrested;  the  heart 
remains  dilated  instead  of  contracted,  and  it  ceases  to  act 
so  long  as  the  current  is  continued.  When  the  current 
ceases  the  heart  soon  begins  to  beat  and  in  a  few  minutes 
will  have  resumed  its  normal  movements.  This  effect  is 
produced  in  most  of  the  inferior  animals  and  can  readily 
be  shown  in  the  frog,  turtle,  alligator  and  other  cold- 
blooded animals,  which  are  well  adapted  to  experiments 
on  the  heart  and  on  the  nerves;  but  in  birds,  Bernard  has 
not  been  able  to  demonstrate  it;  f  for  what  reason,  he  does 
not  state.  When  the  current  is  applied  directly  to  the 
heart,  as  I  have  done  in  some  instances  after  the  organ  has 
been  removed  from  the  chest,  if  the  current  is  suf^ciently 
powerful,  all  regular  pulsations  cease  and  there  is  nothing 
but  the  irregular  vermicular  action  which  is  observed  when 
the  irritability  of  this  organ  has  become  nearly  exhausted. 
This  fact  I  have  observed  in  the  heart  of  the  dog. 

Endeavoring  to  throw  some  light  upon  the  cause  of 
arrest  of  the  heart's  action  by  stimulation  of  the  pneumo- 
gastrics,  I  made  the  following  experiments  upon  the  dog, 
turtle  and  alligator: 

*  Bernard,  "  Substances  toxiques  et  medicamenteuses,"  p.  348. 

f  Bernard,  "Physiologie  et  pathologic  du  systeme  nerveux,"  tome  ii.,  p.  394. 


86    ACTION    OF    THE    HEART    AND    RESPIRATION 

Experiment  XVII. — The  heart  of  a  large  dog  was  exposed  in 
the  usual  way  while  the  animal  was  under  the  influence  of  ether. 
After  the  chest  had  heen  opened  and  while  artificial  respiration  was 
heing  kept  up,  the  pneumogastric  nerves  were  isolated  in  the  neck 
and  a  feehle  current  was  passed  through  them  with  the  magneto- 
electric  machine  used  in  former  experiments. 

The  heart  was  arrested  by  quite  a  feeble  current,  in  the  man- 
ner above  described.  This  was  repeated  several  times.  The  action 
of  the  heart  began  again  when  the  current  was  arrested. 

Experiment  XVIII. — The  heart  of  a  turtle  was  exposed  and 
found  contracting  regularly.  The  pneumogastric  nerves  were  then 
isolated  in  the  neck  and  a  feeble  galvanic  current  passed  through 
thcni.  This  was  done  by  bending  the  ends  of  the  conducting  wires 
in  the  form  of  hooks  and  catching  up  each  nerve.  The  action  of 
the  heart  was  immediately  arrested.  It  began  again  when  the  cur- 
rent was  interrupted  and  stopped  when  it  was  resumed. 

Experiment  XIX.  March  13,  1861. — In  a  medium-sized  dog 
under  the  influence  of  ether  the  carotids  and  pneumogastric  nerves 
were  exposed.  The  cardiometer  was  applied  to  the  right  carotid 
and  the  following  observations  were  made: 

Arterial  pressure  (constant) (Minimum)  125  millimetres. 

At  each  action  of  heart (Maximum)  130  " 

Pulsations 5  " 

The  pneumogastrics  were  then  divided.  The  movements  of  the 
heart  became  more  rapid  and  the  instrument  marked : 

Arterial  pressure  (very  variable) 100  to  150  miUimetres. 

Oscillations  with  heart's  action 2i         " 

The  peripheral  extremities  were  feebly  stimulated.  The  action 
of  the  heart  became  slower  and  the  instrument  marked : 

Minimum 40  millimetres. 

Maximum 65  " 

Pulsations 25  " 

The  current  was  then  stopped  and  the  instrument  marked : 

Minimum I47i-  millimetres. 

Maximum 150  " 

Pulsations 2^  " 

Experiment  XX.  March  11,  1861. — The  pneumogastrics  and 
carotids  were  exposed  in  a  large  dog  in  which  the  chest  had  been 
previously  opened  and  the  heart  exposed  while  the  animal  was 
under  the  influence  of  ether.  The  cardiometer  was  applied  to  the 
right  carotid  and  marked : 

Minimum 40  to  45  millimetres.* 

Maximum 40  to  50  " 

Pulsations 5  " 

*  When  the  chest  is  opened  the  pulsations  become  more  frequent  and  the 
pressure  of  blood  is  much  diminished,  as  is  seen  by  comparing  these  tables  with 
those  in  the  preceding  experiment. 


ACTION    OF    THE    HEART    AND    RESPIRATION    87 


The  pneumogastrics  were  then  feebly  stimulated.  The  pulsa- 
tions of  the  heart  were  diminished  in  frequency  and  the  instru- 
ment marked : 

Pulsations 20  to  30  millimetres. 

Experiments  XVII.  and  XVIII.  demonstrate  the  ar- 
rest of  the  heart's  action  by  stimulation  of  the  pnetmiogas- 
trics  in  the  dog  and  turtle.  This  fact  is  now  established, 
and  the  two  experiments  here  recorded  are  introduced 
merely  to  confirm  previous  observations. 


Explanation  of  Illustration 

The  cardiometer  is  composed  of  a  thick  and  strong  glass 
bottle,  pierced  by  an  iron  tube  securely  soldered,  and 
having  an   opening  (7")  by  which  the  mercury  which 
fills  the  bottle  enters.     One   end  of  the   iron  tube   is 
closed,  the  other  projects  from   the  bottle  and  bends 
upward  in  such  a  way  as  to  receive  at  («')  a  glass  tube 
(7^)  which  is  graduated   and  which   is  -1*2-  to  ^  of  an 
inch  calibre. 
At  the  upper  part  the  bottle  is  hermetically  sealed  by  a 
cork  pierced  by  a  tube  (/)  of  glass  or  iron,  at  the  end 
of  which  is  adjusted  a  metallic  tube  (C)  designed  to 
enter  the  vessel  in  which  it  is  desired  to  measure  the 
pressure.     The  tube  (C)  is  joined  to  the  tube  (/)  by  a 
tube  of  India-rubber  which  should  be  very  short. 
When  the  instrument  is  in  operation  all  of  the  upper  part 
of   the    apparatus   {C  e  t)    is    filled 
with  carbonate  of  soda  in  order  to 
prevent  coagulation  of  the  blood. 
The  level  of  the  mercury  is  (w)  in 
the  bottle,   and   (;/')  in    the    small 
tube.      This    level    corresponds    to 
zero,  and  when  the  blood  presses 
on  the  surface  of  the  mercury  the 
pressure  is  communicated  by  the  opening  ( T)  of  the  iron 
tube  and  the  mercury  ascends  in  the  graduated  glass  tube. 
The  length  of  the  tube  (  T)  should  be  as  great  as  250  milli- 
metres for  powerful  pressures.     (Bernard,   "  Proprietes  et 
alterations  des  liquides  de  I'organisme,  tome  i.,  p.  167.) 

Experiments  XIX.  and  XX.  show  that  when  the  pneu- 
mogastrics are  divided  and  the  action  of  the  heart  is  acceler- 
ated its  force  is  diminished  as  measured  by  the  cardiometer; 
and  that  w'hen  the  action  of  the  heart  is  retarded  by  a  feeble 
current  of  electricity  its  force  is  correspondingly  increased. 
Both  the  arterial  pressure  and  the  pulsations  are  diminished 
in  Experiment  XIX.  by  the  administration  of  ether  and 
very  much  diminished  in  Experiment  XX.  by  the  operation 


88    ACTION    OF    THE    HEART    AND    RESPIRATION 

of  opening  the  chest;  but  my  object  was  merely  to  ol)tain 
the  relative  pressure  and  pulsations,  and  the  effects  of  the 
ether  and  opening  the  chest  did  not  interfere  with  these 
observations,  in  which  I  wished  to  show  that  when  the  pul- 
sations of  the  heart  were  increased  in  number  their  force 
became  diminished,  and  vice  versa. 

The  following  experiments  were  made  in  order  to  de- 
termine the  influence  of  curara  on  this  peculiar  action  on 
the  heart  of  electric  stimulation  of  the  pneumogastrics: 

Experiment  XXI. — A  large  dog  was  poisoned  with  curara 
and  the  heart  exposed  in  the  usual  way.  The  pneumogastric  nerves 
were  then  isolated  and  a  current  of  electricity  passed  through 
them.  The  apparatus  was  the  one  used  in  the  other  experiments; 
and  with  the  most  powerful  current  that  could  be  produced  it  was 
impossible  to  affect  the  action  of  the  heart.  The  animal  had  come 
completely  under  the  influence  of  the  curara. 

Experiment  XXII. — A  large  turtle  was  poisoned  with  curara 
at  I  p.  M.^  and  at  4  p.  m.  was  quite  dead.  The  heart  was  exposed 
>and  found  contracting  regularly.  The  pneumogastric  nerves  were 
then  isolated  in  the  neck  and  a  powerful  current  applied  with  the 
machine  before  mentioned.  It  was  impossible  to  arrest  by  this 
means  the  action  of  the  heart. 

These  experiments,  like  Nos.  XVII.  and  XVIII.,  illus- 
trate many  others  of  a  precisely  similar  character. 

The  experiments  here  detailed  confirm  the  facts  that 
electric  stimulation  of  both  pneumogastrics  will  arrest  the 
movements  of  the  heart  and  that  curara  so  affects  these 
nerves  as  to  abolish  this  action.  This  action  of  curara 
on  the  motor  filaments  is  similar  to  its  action  on  other 
motor  nerves.  Having  an  opportunity  of  operating  upon 
the  alligator  and  wishing  to  repeat  these  experiments  and 
to  observe,  at  the  same  time,  the  action  of  curara  upon  this 
animal,  I  did  so  with  the  following  interesting  results: 

Experiment  XXIII.  November  14,  i860. — An  alligator  more 
than  six  feet  long  was  poisoned  by  the  injection  of  about  three 
grains  of  curara  under  the  skin  of  the  hind  leg.  This  curara  was 
of  an  inferior  quality,  and  the  dose  was  equal  to  about  a  grain  of 
that  made  use  of  in  former  experiments.  In  thirty  minutes  he 
came  sufficiently  under  its  influence  to  be  easily  handled.  The 
chest  was  then  opened  and  the  heart,  which  was  pulsating  regu- 
larly, exposed.  The  animal  was  quite  dead  by  the  time  the  dis- 
section was  finished.  The  pneumogastric  nerves  were  then  exposed 
in  the  neck  and  the  electric  current  was  applied.  The  movements 
of  the  heart  were  arrested  so  long  as  the  current  was  continued 


ACTION    OF   THE    HEART    AND    RESPIRATION    89 

and  began  again  when  it  was  interrupted.  Artificial  respiration 
was  kept  up  for  some  time,  but  this  had  no  effect  upon  the  action 
of  the  heart  and  was  done  merely  to  exhibit  the  play  of  the  lungs. 
The  animal  was  kept  under  observation  three  or  four  hours  and 
the  foregoing  fact  was  repeatedly  verified. 

Experiment  XXIV.  January  28,  1861. — The  above  experi- 
ment was  repeated  upon  another  alligator  of  about  the  same  size 
as  the  first  but  poisoned  with  the  best  quality  of  curara.  In  mak- 
ing the  dissection  for  exposing  the  heart,  a  small  nervous  filament 
going  to  the  sterno-mastoid  muscle  was  exposed,  irritation  of  which 
with  the  scalpel  induced  contraction  of  the  muscle,  though  the 
animal  was  quite  dead.  The  pneumogastric  nerves  were  exposed 
and  the  heart's  action  arrested  by  a  moderate  electric  current.  The 
animal  was  kept  under  observation  more  than  three  hours  and 
this  point  was  repeatedly  verified. 

Twenty-four  hours  after,  the  heart  was  still  beating  vigorously 
and  could  be  arrested  as  before.  The  nervous  filament  going  to 
the  sterno-mastoid  muscle  was  stimulated,  which  produced  slight 
contractions  of  the  muscle.    Muscular  irritability  was  very  marked. 

It  is  only  in  birds  that  experimenters  have  met  with 
any  peculiarity  in  regard  to  the  influence  upon  the  heart  of 
electric  stimulation  of  both  pneumogastric  nerves;  and  in 
proportion  to  their  elevation  in  the  animal  scale,  it  has 
been  difficult,  and  in  most  cases  impossible,  to  arrest  the 
action  of  the  heart  by  the  means  which  will  invariably  pro- 
duce this  efifect  in  mammals,  and  more  easily,  even,  in  cold- 
blooded animals.  Nor  have  any  animals  been  found  able 
to  resist  the  influence  of  the  curara  upon  the  motor  nerves, 
with  the  exception  of  the  alligator.  These  observations 
should  be  extended  to  alligators  of  small  size;  but  as  yet 
I  have  not  been  able  to  procure  them. 

When  I  first  noticed  the  phenomenon  which  I  have 
described,  I  was  at  a  loss  to  account  for  it;  for  the  alligator 
was  motionless  and  insensible  and  the  curara  had  been 
tolerably  prompt  in  its  action,  the  animal  coming  under 
its  influence  in  thirty  minutes  to  three-quarters  of  an  hour 
or  an  hour;  which,  in  a  large  cold-blooded  animal,  where 
the  processes  of  life  are  languid,  is  as  soon  as  one  would 
expect.  In  carefully  reviewing,  however,  my  observations, 
I  found  that  in  the  alligator  the  nervous  system  was  much 
less  affected  by  curara  than  in  other  animals.  In  dogs  the 
motor  nerves  become  entirely  paralyzed  and  death  takes 
place  by  arrest  of  the  muscles  of  respiration;  while  in  the 
alligator,  when  voluntary  movement  and  the  cerebral  func- 
tions are  abolished  so  that  the  animal  can  be  operated  upon 


90    ACTION    OF   THE    HEART    AND    RESPIRATION 

without  the  slightest  difficiiUy,  the  motor  nerves  still  re- 
spond to  stimulation.  In  Experiment  XXIV.  a  nervous 
filament  was  exposed  during  the  operation  and  still  re- 
tained its  irritability,  as  shown  by  muscular  contractions 
when  it  was  irritated  with  the  point  of  the  scalpel.  This 
persisted  and  was  marked,  though  in  a  less  degree  than 
before,  twenty-four  hours  after  death.  The  properties  of 
the  pneumogastrics  remained  with  no  sensible  dimi- 
nution. 

It  is  evident  that  the  motor  properties  of  the  pneumo- 
gastric  nerves,  especially  the  branches  distributed  to  the 
heart,  are  more  important  to  life  than  those  of  ordinary 
motor  nerves  distributed  to  the  general  muscular  system; 
and  it  appears  that  this  nerve  is  protected  from  disturbing 
influences,  like  the  action  of  poison,  to  a  greater  degree 
than  others.  Evidence  of  this  is  seen  in  the  various  sources 
from  which  the  pneumogastric  derives  its  motor  filaments; 
anastomosing,  as  it  does  near  its  origin,  with  the  spinal 
accessory,  the  facial,  the  sublingual  and  the  first  and  sec- 
ond cervicals.  Not  satisfied,  however,  with  this  purely 
anatomical  explanation,  I  endeavored  to  determine  its  pow- 
ers of  resistance  to  poisonous  agents  experimentally.  To 
do  this  I  tried  to  find  some  means  of  retarding  the  ab- 
sorption of  curara,  observing  its  effects  upon  the  nerves 
of  the  animal  from  the  first,  to  determine  whether  its  action 
upon  the  general  motor  system  precedes  that  upon  the 
pnevmiogastric  nerve.  For  this  purpose  I  made  the  fol- 
lowing experiments,  observations  on  the  alligator  not 
being  in  themselves  satisfactory: 

Experiment  XXV.  February  i,  1861. — A  medium-sized  dog 
was  etherized  and  the  chest  opened  in  the  usual  way.  The  opera- 
tion was  done  at  2.15  p.  m.,  and  at  2.40  a  grain  of  curara  dissolved 
in  water  was  injected  under  the  skin  of  the  thigh.  The  sciatic 
nerve  and  both  pneumogastrics  were  then  isolated  and  stimulated. 
By  this  means,  convulsive  movements  were  produced  in  the  leg  and 
the  heart  was  promptly  arrested  by  a  feeble  current. 

At  3.10  the  sciatic  and  pneumogastrics  were  stimulated,  produ- 
cing convulsions  in  the  leg,  not  so  marked  as  before,  and  arresting 
the  action  of  the  heart. 

At  3.40,  one  hour  after  the  injection  of  the  curara,  the  sciatic 
was  found  inexcitable,  but  the  heart  could  be  arrested  by  stimu- 
lation of  the  pneumogastrics,  though  it  required  a  powerful  cur- 
rent. A  weaker  current  diminished  the  frequency  and  increased 
the  force  of  its  pulsations. 


ACTION    OF    THE    HEART    AND    RESPIRATION    91 

At  4.10  the  sciatic  was  still  inexcitable  but  a  powerful  current 
applied  to  the  pneumogastrics  arrested  the  action  of  the  heart. 

Experiment  XXVL  March  11,  1861. — One  grain  of  curara  of 
an  inferior  quality  dissolved  in  water  was  injected  under  the  skin 
of  a  medium-sized  dog.  Twenty-five  minutes  after,  no  effect  being 
produced  by  the  first  injection,  a  second  grain  was  introduced.  In 
ten  minutes  signs  of  poisoning  were  manifested,  the  posterior  ex- 
tremities became  partially  paralyzed  and  the  animal  was  placed 
upon  the  operating  table.  The  chest  was  then  opened  and  the  heart 
exposed,  the  animal  giving  no  evidence  of  pain.  The  pneumogas- 
tric  nerves  were  then  isolated  and  stimulated,  promptly  arresting 
the  action  of  the  heart.  After  the  observation  had  been  continued 
for  about  thirty  minutes  the  animal  partially  recovered  from  the 
influence  of  the  curara  and  made  some  voluntary  movements. 

Aided  by  these  experiments,  it  is  easy  to  understand 
why,  in  the  alHgator,  stimulation  of  the  pneumogastrics 
continued  to  arrest  the  action  of  the  heart  when  the  ani- 
mal had  been  poisoned  with  curara.  The  ahigator  wheti 
undisturbed  breathes  very  slowly;  and  as  in  other  cold- 
blooded animals,  pulmonary  respiration  is  not  necessary 
to  the  movements  of  the  heart.  Curara  seems,  then,  to 
act  first  upon  the  brain,  abolishing  voluntary  motion,  be- 
fore the  motor  nerves  are  paralyzed.  This  was  demon- 
strated in  Experiment  XXV.  on  the  dog;  for  the  effects 
of  the  ether  which  was  administered  before  making  the 
dissection  were  allowed  to  pass  off,  and  the  curara  which 
was  subsequently  administered  abolished  voluntary  motion 
long  before  the  motor  nerves  were  much  affected,  as  dem- 
onstrated by  stimulation  of  the  exposed  sciatic.  The  gen- 
eral motor  nerves  then  slowdy  came  under  its  influence,  and 
last,  the  pneumogastrics,  although  their  action  on  the  heart 
was  not  entirely  abolished.  By  the  means  employed  in  this 
operation,  injecting  the  curara  after  the  vital  powers  had 
been  enfeebled  by  opening  the  chest  and  exposing  the 
thoracic  organs  to  the  cold  air,  the  dog  was  approximated 
to  the  condition  of  the  alligator. 

•  In  Experiment  XXVL,  an  inferior  quality  of  curara 
was  employed,  which  apparently  aboHshed  sensation  and 
volition  but  had  not  sufficient  power  to  entirely  paralyze 
the  general  motor  nerves  and  had  little  or  no  effect  upon 
the  pneumogastrics.  The  specimen  used  had  the  well- 
known  properties  of  ordinary  curara  but  was  deficient  in 
strength. 

From  these  observations  the  followinp-  seems  to  be  the 


92    ACTION    OF   THE    HEART    AND    RESPIRATION 

action  of  curara  upon  the  nervous  system:  It  affects  voli- 
tion and  sensation,  in  whatever  part  of  the  central  nervous 
system  these  functions  reside,  and  the  motor  system  of 
nerves.  In  regard  to  the  order  in  which  various  parts  are 
affected,  first,  sensation  and  voluntary  motion  come  under 
its  influence;  then,  the  general  motor  system  of  nerves; 
and  last,  as  the  preceding  observations  have  demonstrated, 
the  motor  filaments  of  the  pneumogastric  nerves,  especially 
those  which  affect  the  heart.  By  an  ingenious  series  of 
experiments  with  this  substance  upon  frogs,  Bernard  has 
demonstrated  the  fact  that  curara  affects  the  motor  nerves 
exclusively,  leaving  the  sensory  filaments  intact  as  well  as 
the  muscular  system.  He  has  also  shown  that  the  sympa- 
thetic system  is  paralyzed;  for  the  abnormal  heat  and  con- 
gestion which  are  developed  in  the  ear  of  the  rabbit,  for 
example,  when  the  sympathetic  is  divided,  and  which  are 
reduced  to  the  normal  standard  when  the  cut  extremity  is 
faradized,  are  abolished  when  the  animal  is  put  under  the 
influence  of  this  agent.* 

In  the  beginning  of  the  section  devoted  to  the  influence 
of  the  pneumogastrics  upon  the  heart,  I  mentioned  that 
although  the  phenomena  which  follow  stimulation  of  this 
nerve  are  well  established,  no  explanation  of  them  has  yet 
been  given  which  is  generally  accepted.  Many  theories 
have  been  offered  by  physiologists,  but  it  is  not  my  object 
to  discuss  them  here.  I  shall  endeavor  simply  to  give  the 
actual  state  of  knowledge  on  this  subject,  derived  from  the 
experiments  detailed  in  this  essay  and  others  which  are 
generally  accepted. 

I.  The  heart  possesses  in  its  ow-n  fibres  the  property 
of  intermittent  contraction,  and  the  stimulus  of  the  blood 
passing  continually  through  its  cavities  regulates  to  a  cer- 
tain extent  its  movements.  This  is  shown  by  experiments 
in  the  section  on  the  "  Cause  of  the  Rhythmical  Contrac- 
tions of  the  Heart."  Observations  on  the  heart  after  sec- 
tion of  both  pneumogastrics  in  the  neck  show  that  these 
nerves  further  regulate  the  heart's  action;  for  when  their 
influence  is  cut  off,  the  pulsations  of  the  organ  become 
rapid  and  feeble.     This  is  shown  in  Experiment  XIX.,  in 

*  For  a  full  exposition  of  these  facts,  the  reader  is  referred  to  Bernard's 
"  Le9ons  sur  des  substances  toxiques  et  medicamenteuses,"  and  the  "Phys- 
iologic et  pathologic  du  systeme  nerveux." 


ACTION    OF    THE    HEART    AND    RESPIRATION    93 

which  the  pneumogastrics  were  divided  in  the  neck,  in- 
creasing the  rapidity  of  the  heart's  action  but  diminishing 
the  force  of  its  contractions,  as  indicated  by  the  cardio- 
meter.  Many  instances  of  palpitation  of  the  heart  un- 
doubtedly may  be  referred  to  a  deficiency  in  proper  inner- 
vation transmitted  to  it  through  the  pneumogastrics;  for 
most  of  them  are  due  to  derangements  of  the  nervous  sys- 
tem, and  frequently  these  derangements  have  their  origin 
either  in  the  lungs,  from  the  individual  being  put  "  out 
of  breath  "  by  exercise,  or  in  the  stomach,  from  indiges- 
tion, both  being  organs  abundantly  supplied  with  filaments 
from  the  pneumogastric  nerves.  The  phenomena  which 
accompany  palpitation  of  the  heart  are  precisely  those  which 
are  produced  by  section  of  these  nerves. 

II.  When  the  pneumogastrics  in  the  neck  are  stimu- 
lated, the  electric  current  itself  is  not  conducted  by  the 
nerves,  but  there  is  a  stimulus,  resembling  the  ordinary 
*'  nerve  force,"  which  is  conveyed  to  the  muscular  fibres  of 
the  heart.  It  is  difficult,  when  the  irritability  of  the  pneu- 
mogastrics is  unaffected,  to  regulate  the  stimulus  so  as  to 
observe  the  effects  of  sHght  action  of  these  nerves  upon  the 
heart,  its  muscular  tissue  being  extremely  sensitive  to  irri- 
tation of  any  kind;  but  by  the  action  of  curara,  when  it 
partially  paralyzes  the  nerves,  as  in  the  alligator,  or  in  the 
dogs  used  in  Experiments  XXV.  and  XXVI.,  it  can  be 
shown  that  a  slight  stimulus  diminishes  the  frequency  but 
increases  the  power  of  the  contractions  of  the  heart,  w'hile 
a  powerful  stimulus  paralyzes  the  muscular  fibres.  Ex- 
periments XIX.  and  XX.  show  that  when  the  number  of 
the  pulsations  of  the  heart  is  diminished  their  force  is  in- 
creased. If  electricity  is  applied  directly  to  the  heart, 
we  can  equally  paralyze  its  fibres;  and  in  this  instance,  if 
the  current  is  sufficiently  powerful,  this  is  permanent  and 
no  further  regular  contractions  occur.  The  heart,  like 
other  organs,  is  subject  to  various  changes  in  its  nutrition; 
and  if  it  were  not  under  the  control  of  and  regulated  by 
the  pneumogastric  nerves,  it  would  be  subject  to  variations 
in  its  action  which  would  seriously  affect  the  general  sys- 
tem. A  certain  amount  of  nerve-force,  like  the  "  muscu- 
lar sense  "  which  produces  tonicity  of  the  muscular  system, 
is  continually  supplied  to  it  by  the  cerebro-spinal  system, 
which  regulates  and  moderates  its  action;  this  can  be  close- 


94    ACTION    OF   THE    HEART   AND    RESPIRATION 

]y  imitated  by  electricity;  a  slight  current  merely  moderates 
the  action  of  the  heart,  but  a  powerful  current,  which  repre- 
sents the  nerve-force  in  an  intensely  exaggerated  form,  ar- 
rests its  action  completely.  It  is  not  surprising  that  an 
organ  which  possesses  such  ])eculiarity  in  the  properties 
of  its  muscular  structure  and  the  proper  action  of  which  is 
so  important  to  the  well-being  and  the  life  of  the  animal 
should  be  thus  guarded  by  the  nervous  system.  There  are 
instances  on  record  of  immediate  death  by  stoppage  of  the 
heart  from  fright,  anger,  grief  and  other  severe  mental  emo- 
tions which  operate  powerfully  on  the  nervous  system. 
Syncope  from  these  causes  is  by  no  means  uncommon.  In 
the  latter  instance,  when  the  heart  resumes  its  functions, 
the  nervous  shock  carried  along  the  pneumogastrics  has 
been  sufficient  only  to  temporarily  arrest  the  action  of 
the  heart;  in  the  former,  when  death  is  the  result,  the  shock 
has  been  so  great  that  the  heart  is  unable  to  recover  from 
its  effects. 

Mechanism  of  the  Closure  of  the  Valves  of  the 
Heart. — The  four  ventricular  orifices  of  the  heart  are  pro- 
vided with  valves  which  permit  the  blood  to  flow  in  only 
one  direction.  In  some  of  the  inferior  animals  the  auricu- 
lar orifices,  by  which  the  blood  passes  from  the  veins  into 
the  heart,  are  provided  with  valvular  apparatus.  This  is 
the  case  in  fishes;  but  in  animals  which  have  a  double  heart 
and  in  man,  the  openings  of  the  great  veins  into  the  right 
auricle  and  of  the  pulmonary  vein  into  the  left  auricle  are 
not  provided  with  valves.  These  orifices  are  narrowed, 
however,  by  the  contraction  of  the  fibres  during  the  auric- 
ular systole,  moderating,  though  not  entirely  preventing 
regurgitation;  while  the  play  of  the  auriculo-ventricular 
valves  permits  the  blood  to  flow  freely  in  and  fill  the  ven- 
tricles. The  ventricles  then  contract  powerfully,  close  the 
auriculo-ventricular  valves,  force  open  the  semilunar  valves 
and  project  the  blood,  on  the  one  side,  into  the  pulmo- 
nary artery,  and  on  the  other  into  the  aorta;  from  whence 
it  is  immediately  prevented  from  regurgitating  by  the 
closing  of  the  aortic  and  pulmonary  valves.  Thus  the 
blood,  forced  into  the  right  auricle  from  the  veins  of 
the  system,  moves  in  but  one  direction  toward  the  aorta 
and    is    prevented    from    taking    a    backward    course    by 


ACTION    OF    THE    HEART    AND    RESPIRATION    95 

the  valves  which  protect  the  orifices  of  both  ventri- 
cles. It  is  correctly  stated  by  physiological  writers  that 
the  tricuspid  valves,  unlike  the  mitral,  do  not  always 
completely  close  the  right  auriculo-ventricular  orifice. 
This  may  be  observed  in  a  very  simple  experiment. 
Taking  the  fresh  heart  of  any  animal,  the  bullock,  for  ex- 
ample, cutting  away  the  left  auricle  and  forcing  water  into 
the  ventricle  with  a  syringe  introduced  into  the  aorta,  the 
aortic  valves  having  been  previously  destroyed,  it  will  be 
seen  that  the  mitral  valve  effectually  prevents  the  flow  of 
the  water  through  the  auriculo-ventricular  opening;  and 
the  free  borders  of  valves,  the  action  of  which  may  thus 
be  exhibited,  are  closely  and  effectually  brought  together 
by  the  pressure  exerted  against  them.  But  if  an  analogous 
experiment  is  performed  upon  the  right  side  of  the  heart, 
cutting  away  the  right  auricle  so  as  to  expose  the  tri- 
cuspid valves  and  injecting  water  against  them  through 
the  pulmonary  artery,  it  will  be  seen  that  a  slight  regur- 
gitation takes  place  and  that  these  valves  do  not  so  effec- 
tually close  the  auricular-ventricular  orifice.  Mr.  T.  W. 
King,  in  an  essay  published  in  "  Guy's  Hospital  Reports  " 
for  1837,  pointed  out  the  peculiarity  of  action  of  the  tri- 
cuspid valves  and  called  it  the  "  safety-valve  function  of 
the  right  ventricle."  He  stated  that  it  was  a  provision  to 
prevent  congestion  of  the  lungs  when  anything  occurred 
to  obstruct  the  pulmonary  circulation;  and  it  is  evident 
that  by  this  means,  the  delicate  tissue  of  the  lungs,  in  which 
congestion  can  not  be  relieved  by  anastomoses  as  in  the 
general  circulation,  may  be  protected  from  injurious  accu- 
mulation or  pressure  of  blood.  The  difference  between 
the  action  of  these  valves  on  the  two  sides  of  the  heart  I 
have  repeatedly  verified,  and  it  can  be  easily  demonstrated 
in  the  manner  just  described. 

The  next  question  which  presents  itself  is  the  follow- 
ing: By  what  means  are  the  valves  of  the  heart  made  to 
close?  This  question  may  be  easily  answered  in  regard  to 
the  semilunar  valves.  The  blood  circulates  in  the  arterial 
system  under  a  pressure  which  will  support  a  column  of 
about  six  feet  of  water  or  six  inches  of  mercury.  During 
the  flow  of  blood  from  the  ventricle  into  the  aorta,  the 
power  of  the  heart  overcomes  this  pressure  and  opens  the 
valves;  but  when  the  force  of  the  heart  is  taken  off,  the 


96    ACTION    OF    THE    HEART    AND    RESPIRATION 

valves  are  closed,  effectually  preventing  regurgitation. 
One  would  naturally  suppose  that  the  auriculo-ventricular 
valves  were  closed  in  the  same  way,  by  backward  pressure; 
and  this,  indeed,  is  the  general  opinion;  but  in  1843,  Baum- 
garten  endeavored  to  prove  by  experiment  that  these 
valves  are  closed  by  a  current  in  another  direction,  at- 
tributing it  to  a  contraction  of  the  auricles  and  not  the 
action  of  the  ventricles.  I  do  not  know  that  this  view  has 
met  with  much  favor,  but  some  observers  have  confirmed 
his  experiments,  and  the  explanation  has  been  adopted 
by  Milne  Edwards  *  and  a  few  others.  The  experiments 
upon  which  this  view  is  based  are  briefly  these: 

The  heart  of  a  large  warm-blooded  animal  is  prepared 
by  completely  removing  the  auricles  so  as  to  expose  the 
auriculo-ventricular  valves.  It  is  then  held  in  a  vertical 
position,  the  valves  lying  in  the  cavity  of  the  ventricles, 
leaving  the  orifice  patent.  If  water  is  poured  slowly  into 
one  of  the  ventricles  through  this  opening,  the  valves  will 
gradually  fioat  out  and  their  edges  approximate;  then, 
when  the  ventricle  is  nearly  filled,  if  the  stream  is  suddenly 
increased  in  power,  the  valves  completely  close. 

The  facts  here  stated  are  entirely  correct,  and  I  have 
repeatedly  verified  them;  but  if,  as  before  stated,  a  stream 
of  water  is  forced  against  the  valves,  the  orifice  is  closed. 
One  can  not,  therefore,  reason  from  the  experiments  of 
Baumgarten  that  this  is  the  natural  mechanism  of  the  clo- 
sure of  the  valves,  but  it  is  necessary  to  examine  the  condi- 
tions as  they  exist  in  the  normal  relations  of  the  organ. 
For  that  purpose,  and  with  the  object  of  settling  this  ques- 
tion if  possible,  I  carefully  repeated  the  experiments  of 
Baumgarten  and  carried  his  observations  a  little  farther. 

Experiment  XXVII.  January  30,  1861. — In  this  experiment  I 
found  that  the  mitral  valves  were  closed  when  the  current  of  water 
poured  into  the  ventricle  flowed  in  a  small  stream.  In  this  case 
it  is  evident  that  they  were  closed  by  backward  pressure ;  for  the 
current  of  water,  flowing  thus  in  a  bullock's  heart  prepared  in  the 
manner  above  described,  did  not  exert  pressure  upon  the  whole 
of  the  auricular  face  of  the  valves,  but  merely  made  a  small  open- 
ing for  itself  between  them.  I  then  used  a  larger  stream,  and  in 
this  instance  the  valves  were  overpowered,  and  the  water  flowed 
in  a  full   stream   from  the  aorta.     The  aortic  opening  was  then 

*  Milne  Edwards,  "  Lecons  sur  la  physiologic  et  Tanatomie  comparee  de 
rhomme  et  des  animaux,"  tome  iv.,  p.  30. 


ACTION    OF   THE    HEART  AND    RESPIRATION    97 

closed  and  regurgitation  took  place  freely  at  the  auriculo-ventric- 
ular  orifice.  In  this  modification  of  the  experiment,  however,  the 
force  of  the  water  was  considerably  greater  than  that  of  the  natural 
current  of  blood.  It  was  impossible,  indeed,  to  graduate  this,  and 
to  pour  the  fluid  into  the  ventricle  in  a  stream  which  would  im- 
pinge upon  the  entire  surface  of  the  valves,  which  did  not  flow 
with  considerable  force.  These  facts  were  repeatedly  verified  in 
this,  and  in  confirmatory  experiments  which  it  is  unnecessary  to 
detail  here. 

We  may  now  consider  the  pressure  of  the  blood  in  the 
cavities  of  the  heart  during  circulation;  for  it  is  evident 
that  when  the  auricle  is  entirely  removed  and  water  is 
poured  from  a  height  into  the  ventricle,  the  experiment 
is  far  from  fulfilling  the  natural  conditions,  which  it  is  so 
necessary  to  observe  in  all  physiological  observations. 
During  the  normal  circulation,  the  veins,  heart  and  arteries 
are  completely  filled  with  blood;  no  air  or  gas  can  exist, 
except  in  solution,  in  the  circulatory  system;  and  espe- 
cially in  the  heart  does  the  presence  of  any  gaseous  fluid 
disturb  the  circulatory  function.  The  blood,  also,  circu- 
lates under  a  certain  pressure;  and  a  certain  force  is  ex- 
erted by  the  heart  at  every  pulsation.  In  the  arterial  sys- 
tem the  pressure  of  the  blood  is  represented  by  a  column 
of  six  inches  of  mercury.  This  pressure  is  nearly  constant 
in  the  arteries  but  is  intermittent  in  the  heart.  In  the  heart 
the  pressure  is  nil  during  diastole,  as  has  been  shown  by 
actual  experiment,*  but  nearly  one-third  greater  than  the 
arterial  pressure  during  its  systole.  In  the  venous  system 
the  pressure  is  much  less  constant  than  in  the  arteries;  it  is 
always  less,  and  subject  to  frequent  variations.  Bernard 
found  the  arterial  pressure  in  the  carotid  of  the  horse, 
measured  by  the  cardiometer,  to  be  no  millimetres.  At 
each  cardiac  pulsation  it  was  increased  to  lyS-f  I^  ^^" 
other  horse  he  found  the  pressure  in  the  jugular  to  vary 
between  105,  100,  95  and  90  millimetres.:}:  The  pressure 
exerted  by  the  contraction  of  the  auricles  has  not  been 
ascertained;  and  although  it  adds  something  to  the  venous 
pressure,  it  can  not  be  very  considerable.  Under  these 
conditions,  during  the  diastole  of  the  ventricles,  the  venous 
pressure  operates  upon  the  auricular  face  of  the  auriculo- 

*  Bernard,    "  Le9ons   sur   les   proprietes   physiologiques   et   les  alterations 
pathologiques  des  liquides  de  I'organisme,"  tome  i.,  p.  173. 

f  Bernard,  ^/.  n't.,  p.  172.  |  Bernard,  oJ>.  at.,  p.  203. 

7 


98    ACTION    OF   THE    HEART   AND    RESPIRATION 

ventricular  valves,  it  has  no  cardiac  pressure  to  oppose  it 
and  the  orifice  is  kept  patent.  The  same  is  true  during  the 
contraction  of  the  auricles;  the  pressure  is  thereby  in- 
creased, it  is  exerted  by  a  column  of  blood  which  impinges 
upon  the  entire  surface  of  the  valves  and  the  ventricles 
are  thus  completely  filled.  During  this  time  the  blood  is 
prevented  from  regurgitating  from  the  aorta  and  pulmo- 
nary artery  by  the  semilunar  valves,  which  are  closed  by 
the  arterial  pressure.  But  when  the  ventricles  act,  they 
exert  a  force  sufficient  to  overcome  the  arterial  pressure, 
which  keeps  the  semilunar  valves  closed;  and  at  the  same 
time  they  close  the  auriculo-ventricular  valves,  producing 
one  element  of  the  first  sound  of  the  heart.  The  systole  of 
the  ventricles  ceases;  its  pressure  is  taken  ofY;  the  arterial 
pressure  closes  the  semilunar  valves,  producing  the  second 
sound;  the  venous  pressure  opens  the  auriculo-ventricular 
valves,  and  keeps  the  orifice  patent,  until  the  succeeding 
contraction  of  the  ventricles.  Thus  it  is  that  the  cardiac 
pressure,  intermittent  and  operating  during  the  systole  of 
that  organ,  being  greater  than  the  arterial  and  venous 
pressure,  at  the  same  time  opens  the  semilunar  and  closes 
the  auriculo-ventricular  valves. 

Inasmuch  as  Baumgarten's  experiments  showed  that 
the  auriculo-ventricular  valves,  which  are  closed  by  means 
of  a  backward  pressure  during  the  systole  of  the  ventricles, 
can  be  closed  by  pouring  a  stream  of  water  into  the  ventri- 
cles from  the  auricles,  it  occurred  to  me  to  extend  these 
observations  to  the  aortic  semilunar  valves,  and  for  this 
purpose  I  made  the  following  experiment: 

Experiment  XXVIII.  January  30,  1861. — A  bullock's  heart 
was  prepared  so  as  to  show  the  action  of  the  aortic  valves;  which 
was  done  by  cutting  away  a  portion  of  the  left  ventricle  so  as  to 
expose  them  to  view,  securing  the  nozzle  of  a  large  syringe  in  the 
aorta  and  forcing  water  toward  the  ventricular  cavity.  The  semi- 
lunar valves  were  thus  closed,  effectually  preventing  the  passage 
of  the  fluid.  While  the  nozzle  was  yet  in  the  aorta,  diminishing 
but  not  preventing  the  flow  of  liquid,  water  was  poured  from  a  con- 
siderable height  into  the  vessel.  The  valves  were  at  first  floated 
out  and  then  closed  in  the  same  manner  as  in  Experiment  XXVII. 
on  the  mitral  valves.    This  observation  was  repeatedly  verified. 

This  last  experiment  would  go  as  far  to  prove  that 
the  semilunar  valves  are  closed  by  a  current  from  the  ven- 
tricle into  the  aorta,  as  the  preceding  one  does  that  the 


ACTION    OF    THE    HEART    AND    RESPIRATION 


99 


current  from  the  auricle  to  the  ventricle  closes  the  mitral 
valves;  yet,  I  venture  to  assert,  no  one  could  entertain  for 
a  moment  the  view  that  the  force  which  overcomes  the 
resistance  of  the  aortic  valves,  by  operating  from  the  ven- 
tricles, closes  them  by  the  same  current.  The  experiment, 
of  course,  proves  nothing  in  regard  to  the  action  of  the 
valves  at  the  aortic  orifice,  but  it  shows  the  falsity  of  con- 
clusions drawn  from  experiments  in  which  natural  condi- 
tions are  so  utterly  disregarded  as  in  those  which  favor 
the  idea  that  valves  arranged  for  the  purpose  of  permitting 
the  flow  of  blood  in  one  direction  and  preventing  reflux 
are  closed  by  the  opposite  current.* 

Seat  of  the  Sensation  of  the  "  Besoin  de  res- 
pirer,"  which  gives  rise  to  the  movements  of  res- 
PIRATION.— The  circulation  of  the  blood  is  intimately  con- 
nected with  the  function  of  respiration.  In  health  the 
number  of  pulsations  of  the  heart  bears  a  definite  relation 
to  the  number  of  the  respiratory  movements;  when  the 
pulse  is  increased  in  frequency,  the  breathing  is  more  rapid; 
and  when  the  heart  labors,  as  in  cases  of  advanced  disease 
of  this  organ,  the  patient  experiences  a  sense  of  suffoca- 
tion which  is  not  dependent  upon  the  condition  of  the  re- 
spiratory organs.  What  gives  rise  to  this  sense  of  suffo- 
cation? Why  is  it,  when  the  lungs  are  unaffected  and 
when  a  large  supply  of  pure  air  is  taken  in  at  every  respir- 
atoiy  act,  that  a  sense  of  suffocation  attends  imperfect 
action  of  the  heart  ?  These  are  questions  which  are  of  great 
interest  to  the  pathologist;  but  they  can  not  be  answered 
without  a  knowledge  of  the  seat  of  sensation  of  want  of 
air,  which  ordinarily  is  not  perceived  by  the  brain  but  in- 
sensibly induces  respiratory  movements,  and  when  circu- 
lation or  respiration  is  much  disturbed,  gives  rise  to  the 
distressing  sensation  of  suffocation.  To  resolve  these 
questions,  which  are  as  yet  imperfectly  or  incorrectly  an- 
swered by  physiologists,  is  the  object  of  this  division  of  the 
present  paper. 

Respiratory  movements  are  regarded  as  reflex,  a  cer- 

*  Since  this  paper  was  written,  I  have  seen  a  short  article  on  the  method 
and  time  of  closure  of  the  auriculo-ventricular  valves,  by  Dr.  Halford  ;  but  the 
experiments  seem  to  prove  nothing  beyond  those  here  mentioned,  being,  indeed, 
little  more  than  repetitions. 


loo    ACTION    OF    THE    HEART    AND    RESPIRATION 

tain  impression  being  conveyed  to  the  respiratory  centre, 
followed  by  the  action  of  the  inspiratory  muscles.  This  is 
partly  under  control  of  the  will;  but  under  ordinary  cir- 
cumstances is  involuntary.  It  is  unnecessary  to  enter  into 
any  discussion  in  regard  to  the  seat  of  the  respiratory  cen- 
tre. Physiologists  now  agree  that  it  is  situated  in  the  me- 
dulla oblongata  at  about  the  origin  of  the  pneumogastric 
nerves.  Almost  the  same  unanimity  exists  in  regard  to 
the  localization  of  the  impression  which  gives  rise  to  the 
inspiratory  acts;  attributing  it  to  an  impression  made  upon 
filaments  of  the  pneumogastric  nerves  by  the  carbonic  acid 
in  the  air-cells.  This  is  the  view  which  was  advanced  by 
Marshall  Hall  and  which  is  now  generally  adopted;  but 
there  are  difficulties  in  the  way  of  explaining  all  the  phe- 
nomena which  are  observed  in  health  and  disease  on  this 
theory.  In  diseases  of  the  heart  there  may  be  dyspnoea, 
and  yet  the  air  be  rapidly  and  efficiently  changed  in  the 
lungs.  The  evolution  of  a  large  quantity  of  carbonic  acid 
by  the  lungs,  if  it  is  promptly  exhaled,  does  not  produce 
dyspnoea.  In  experiments  upon  the  lower  animals,  which 
are  to  be  mentioned  hereafter,  phenomena  are  developed 
for  which  such  an  explanation  will  not  suffice.  There  are 
some  physiologists,  indeed,  who  do  not  accept  this  ex- 
planation of  Marshall  Hall;  among  them  are  Berard,  who 
locates  the  sense  of  want  of  air  in  the  heart;  *  John  Reid, 
who  thought  that  the  respiratory  movements  were  due  to 
the  action  of  the  black  blood  upon  the  medulla  oblongata; 
Volkmann  and  Vierordt,  who  thought  that  these  move- 
ments were  reflex  and  due  to  the  excitation  of  the  general 
sensory  system  of  nerves  by  venous  blood.  This  is  a  ques- 
tion, however,  which  may  be  settled  by  direct  experiment. 
If  a  dog  is  rendered  insensible  by  ether  and  the  chest 
opened,  artificial  respiration  being  kept  up  by  a  pair  of 
bellows,  he  will  make  no  respiratory  movements  so  long 
as  respiration  is  carried  on  artificially;  but  soon  after  res- 
piration is  stopped,  the  diaphragm,  intercostals  and  other 
inspiratory  muscles,  which  are  actually  denuded  and  ex- 
posed to  view,  will  be  seen  to  contract  violently,  this  con- 
traction, or  effort  at  respiration,  ceasing  so  soon  as  arti- 
ficial respiration  is  resumed. 

*  Berard,  "  Cours  de  physiologic,"  tome  iii.,  p.  523. 


ACTION    OF    THE    HEART    AND    RESPIRATION    loi 

An  experiment  analogous  to  this  was  performed  in 
1664,  by  Robert  Hooke,  in  which  he  demonstrated  that 
respiratory  efforts  ceased  in  an  animal  so  long  as  the  requi- 
site quantity  of  air  was  supplied  to  the  lungs.  In  this  ex- 
periment he  made  an  opening  into  the  pleural  cavity  and 
the  lungs  of  a  living  dog  and  forced  a  current  of  air  through 
the  trachea  and  out  at  the  artificial  opening.  So  long  as 
the  current  was  continued  the  animal  remained  quiet;  but 
when  it  was  interrupted  he  made  efforts  at  respiration. 
This  experiment  is  made  use  of  by  Marshall  Hall  to  sup- 
port his  doctrine  of  the  reflex  character  of  respiration,  the 
excitation  coming  from  the  lungs;  for,  he  says,  so  long  as 
fresh  air  was  supplied  to  the  lungs  there  was  no  stimulus 
for  respiration  and  therefore  no  efforts  were  made;  but 
when  this  current  ceased  or  when  carbonic  acid  was  sub- 
stituted for  atmospheric  air,  the  contact  of  the  carbonic 
acid,  which,  in  the  one  instance,  was  exhaled  by  the  venous 
blood,  and  in  the  other  was  introduced  into  the  lungs,  pro- 
duced the  excitation  which  was  necessary  to  the  respira- 
tory act.  This,  however,  is  but  a  superficial  view  of  these 
phenomena.  It  is  necessary  to  examine  into  the  condition 
of  the  heart  and  the  rest  of  the  circulatory  system.  It  is 
well  known  that  the  heart's  action  is  dependent  upon  res- 
piration and  that  an  arrest  of  the  interchange  of  gases  in 
the  lungs  is  immediately  felt  by  the  circulation.  It  was  for 
the  purpose  of  observing  these  conditions  that  the  follow- 
ing experiments  were  made: 

Experiment  XXIX.  February  16,  1861. — A  medium-sized 
dog  was  etherized  and  the  heart  and  lungs  exposed  in  the  visual 
way.  A  pair  of  bellows  was  introduced  into  the  trachea  and  arti- 
ficial respiration  kept  up.  So  long  as  this  was  performed,  the  ani- 
mal made  no  efforts  at  respiration,  even  after  he  had  almost  recov- 
ered from  the  effects  of  the  anesthetic;  but  when  the  artificial  res- 
piration was  stopped,  he  soon  began  to  make  efforts  to  breathe, 
as  was  indicated  by  contractions  of  the  diaphragm  and  intercostals, 
which  were  exposed  to  view.  The  femoral  artery  was  then  isolated 
and  divided,  a  ligature  applied  to  the  distal  end.  and  the  cardiac 
end  compressed  with  the  fingers  so  that  the  blood  could  be  permitted 
to  flow  at  will.  A  small  stream  was  then  allowed  to  escape,  which 
was  of  the  brilliant  red  color  of  arterial  blood,  the  animal  remain- 
ing quiet  and  respiration  being  kept  up  actively.  Respiration  was 
then  stopped,  and  the  animal  remained  auiet  until  the  blood  be- 
came dark  in  the  exposed  artery.  He  then,  and  not  until  then, 
began  to  make  eft'orts  at  respiration.    Respiration  was  now  resumed 


I02    ACTION   OF   THE    HEART    AND    RESPIRATION 

and  the  blood  gradually  became  red.  The  animal  continued  to 
make  efforts  at  respiration  until  the  blood  became  red  in  the  artery. 
This  observation  was  frequently  repealed  and  the  above  phenome- 
na were  invariable.  Since  that  time,  also,  I  have  repeated  the  ex- 
periment upon  other  animals,  always  with  the  same  result. 

Experiment  XXX.  February  19,  1861. — A  good-sized  dog  was 
poisoned  with  curara  and  the  chest  opened  in  the  usual  way.  When 
the  animal  came  fully  under  the  influence  of  the  poison  he  ceased 
all  respiratory  movements.  Artificial  respiration,  however,  was 
kept  up  for  three  hours ;  and  in  about  two  and  a  half  hours  he 
had  so  far  recovered  from  the  effects  of  the  poison  as  to  make 
efforts  at  breathing  when  artificial  respiration  was  interrupted. 
The  femoral  artery  was  then  opened  and  divided  as  in  the  former 
experiment.  When  respiration  was  arrested  the  animal  made  ef- 
forts to  breathe,  but  only  when  the  blood  became  dark  in  the  artery, 
and  ceased  these  efforts  when  it  became  red  again  on  resuming 
respiration.     This  observation  was  made  repeatedly.* 

Experiment  XXXI.  February  15,  1861. — In  a  large  dog  un- 
der the  influence  of  ether,  in  which  the  heart  was  beating  regu- 
larly, the  organ  was  suddenly  cut  from  the  chest.  The  animal 
afterwards  made  several  respiratory  movements.  In  this  instance 
the  "  besoin  de  respirer  "  could  not  be  derived  from  the  heart,  as 
it  had  been  removed  from  the  body. 

Experiment  XXXII.  March  11,  1861. — A  good-sized  dog  was 
etherized  and  the  heart  exposed  in  the  usual  way.  Artificial  respi- 
ration was  actively  kept  up,  and  while  the  heart  was  pulsating 
regularly  and  vigorously,  it  was  cut  from  the  chest  by  a  single 
sweep  of  the  knife.  The  lungs  were  still  regularly  inflated,  but  in 
thirty  seconds  the  animal  began  to  make  efforts  at  respiration, 
which  were  continued  for  two  and  a  quarter  minutes.  These  ef- 
forts were  powerful  and  convulsive. 

It  would  seem  settled  by  these  experiments,  that  the 
"  besoin  de  respirer,"  which  is  conducted  to  the  respiratory- 
centre  and  excites  the  movements  of  respiration,  is  not 
situated  in  the  lungs  or  in  the  heart  but  in  the  general  sys- 
tem; and  the  sense  of  suffocation  is  due  to  the  presence  of 
black  or  venous  blood  in  tissues  which  should  be  supplied 
with  arterial  blood.  One  would  therefore  expect  that  this 
peculiar  sensation  would,  if  it  resided  in  the  general  sys- 
tem, be  conveyed  to  the  nerve-centres  by  the  ordinary 
sensory  nerves  and  not  by  the  pneumogastrics,  as  was  sup- 

*  This  experiment  has  additional  interest  as  confirming  the  well  known  ex- 
periments of  Brodie,  in  which  he  demonstrated  that  in  poisoning  by  certain 
substances,  their  eiTects  will  pass  off  if  artificial  respiration  is  continued  for 
a  certain  time.  Among  these  poisons  are  curara  and  opium.  Of  course,  in 
this  instance,  it  would  have  been  impossible  to  preserve  the  life  of  the  animal 
after  the  chest  had  been  opened  and  the  thoracic  organs  exposed,  but  he  evi- 
dently recovered  considerably  from  the  effects  of  the  poison. 


ACTION    OF   THE    HEART    AND    RESPIRATION    103 

posed  by  Marshall  Hall.     This,  indeed,  is  the  fact,  as  is 
shown  by  the  following  experiment: 

Experiment  XXXIII.  February  15,  1861. — A  medium-sized 
•dog  was  etherized  and  the  heart  and  lungs  exposed  in  the  usual 
way.  The  occurrence  of  respiratory  efforts  when  the  blood  be- 
came black  in  the  arteries  and  their  cessation  so  soon  as  it  regained 
its  red  color  were  noted.  The  pneumogastric  nerves  were  then 
isolated  in  the  neck  and  divided,  producing  the  usual  effect  upon 
the  movements  of  the  heart.  The  experiments  of  arresting  artifi- 
cial respiration  and  exciting  respiratory  efforts  on  the  part  of  the 
animal  were  then  repeated  with  precisely  the  same  effect  as  before 
division  of  the  pneumogastrics  and  as  observed  in  other  experi- 
ments. 

Although  the  sense  which  induces  respiration  is  thus 
located  in  the  tissues  and  it  is  shown  that  it  does  not  re- 
side in  the  organs  of  respiration  themselves,  the  cause  of 
this  impression  does  not  appear.  The  venous  blood  either 
irritates  the  system  from  the  presence  of  elements  which 
are  not  contained  in  the  same  proportion  in  arterial  blood 
or  the  tissues  feel  the  want  of  some  principle  which  the 
venous  blood  does  not  contain  in  sufficient  quantity.  The 
great  difference  between  venous  and  arterial  blood  is  in  the 
quantity  of  oxygen  which  they  contain.  According  to  the 
latest  experiments  of  Bernard  in  regard  to  the  compara- 
tive quantity  of  oxygen  in  arterial  and  venous  blood,  it 
appears  that  the  arterial  blood  of  a  healthy  dog  contained 
18.28  parts  of  oxygen  for  every  hundred  parts  of  blood, 
while  venous  blood  contained  only  8.42  parts  of  oxygen 
per  hundred.*  In  these  experiments  Bernard  found  that 
when  the  gas  was  estimated  by  displacement  with  hydro- 
gen or  nitrogen,  it  became  diminished  if  allowed  to  stand 
a  few  hours,  and  that  part  of  the  oxygen  became  united 
with  carbon  to  form  carbonic  acid.  He  employed  carbonic 
oxide  as  a  displacing  agent,  which  prevented  this  change; 
hence  the  large  proportion  of  oxygen  which  he  foimd  in 
both  varieties  of  blood.  The  usual  estimates  are  based 
upon  the  experiments  of  Magnus  and  indicate  in  the  arte- 
rial blood  of  five  animals  (three  horses  and  two  calves) 
separately  examined,  a  mean  of  2.44  per  cent,  of  oxygen 
for  arterial,  and  1.15  per  cent,  for  venous  blood,  an  esti- 
mate very  far  short  of  the  truth.    The  venous  blood  is  sup- 

*  Bernard,    "  Le9ons  sur  les   propri^tes   physiologiques,  et   les   alterations 
pathologiques  des  liquides  de  Torganisme,"  tome  i.,  p.  367. 


I04    ACTION    OF    THE    HEART    AND    RESPIRATION 

posed  by  Brown-Sequard  and  others  to  be  an  active  stimu- 
lant to  the  tissues  on  account  of  its  irritating  properties; 
but  when  it  is  shown  that  the  arterial  blood  contains  such 
a  large  proportion  of  oxygen,  which  is  indispensable  to  the 
system  and  is  contained  in  small  quantity  in  the  non- 
arterialized  blood,  the  immediate  inquiry  is  as  to  whether 
the  excitation  in  question  is  due  to  the  stimulating  proper- 
ties of  the  venous  blood  or  the  want  of  oxygen  in  the 
tissues,  which  latter  can  be  supplied  only  by  arterial  blood. 
This  question  I  conceive  can  be  settled  by  experiment. 
An  animal  does  not  feel  the  "  besoin  de  respirer  "  while 
artificial  respiration  is  kept  up  actively;  but  he  does  soon 
after  this  process  is  interrupted.  In  this  case,  partially  oxy- 
genated blood  circulates  in  the  arteries  and  is  supplied  to 
the  systemic  capillaries.  If  it  be  that  the  tissues  simply 
need  oxygen,  any  cause  which  w'ould  prevent  oxygen  from 
coming  in  contact  with  them  would  give  rise  to  respiratory 
movements,  though  there  is  no  black  blood  in  the  arteries 
and  an  abundant  supply  of  fresh  air  is  introduced  into  the 
lungs.    The  following  experiment  bears  upon  this  point: 

Experiment  XXXIV.  February  19.  1861. — A  good-sized  dog- 
was  etherized  and  the  chest  opened  in  the  usual  way.  Artificial 
respiration  was  established  and  Experiment  XXIX.  verified.  The 
blood  was  then  allowed  to  flow  freely  from  the  femoral  artery 
while  artificial  respiration  was  actively  continued.  While  the  blood 
continued  to  flow  the  respiratory  muscles  were  carefully  observed. 
During  the  first  part  of  the  bleeding,  no  respiratory  efforts  took 
place ;  but  when  the  blood  had  flowed  for  a  considerable  time  and 
the  system  was  becoming  drained,  respiratory  efforts  began,  feeble 
at  first,  but  as  the  bleeding  continued,  becoming  more  violent  until 
the  whole  muscular  system  was  affected  with  convulsive  movements. 

This  experiment  is  of  great  interest  and  importance. 
By  the  withdrawal  of  blood  while  respiration  was  active 
the  tissues  were  deprived  of  oxygen  by  a  diminution  in 
the  quantity  of  blood,  and  were  relieved  from  the  stimula- 
tion of  the  black  blood,  if  it  has  any  stimulating  properties, 
for  all  the  blood  going  to  the  capillaries  was  purely  arterial 
in  character.  No  stimulation,  then,  was  applied  to  the 
tissues;  they  simply  were  deprived  of  their  normal  supply 
of  oxygen  by  a  diminution  of  the  oxygen-carrying  fluid. 
This  gave  rise  to  the  "  besoin  de  respirer,"  first  to  a  slight 
extent,  but  as  the  hemorrhage  continued,  increasing  in 
intensity  till  the  whole  muscular  system  was  convulsed 


ACTION    OF    THE    HEART   AND    RESPIRATION    105 

from  the  overpowering  sense  of  suffocation;  a  sense  which 
is  referred  to  the  lungs  but  which  really  resides  in  the  gen- 
eral system. 

These  experiments  give  a  new  view  of  the  "  besoin  de 
respirer,"  which  gives  rise  to  the  respiratory  movements, 
and  of  the  sense  of  suffocation,  which  is  incident  to  the  in- 
terruption of  these  movements.  Alore  and  more  as  knowl- 
edge of  the  functions  of  the  body  advances  are  certain  sen- 
sations which  seem  to  come  from  special  organs  actually 
located  in  the  general  system. 

In  treating  of  the  sensation  now  under  consideration 
I  am  led  to  compare  it  with  various  others  that  are  famil- 
iar. The  system  needs  periodical  rest;  it  is  undergoing 
an  incessant  waste  which  must  be  supplied  by  food,  and 
a  continual  loss  of  fluid  which  must  be  supplied  by  water; 
and  it  needs  a  constant  supply  of  oxygen,  which  is  furnished 
by  respiration.  These  are  wants  of  the  general  system; 
but  their  indications  are  referred  to  particular  parts. 
Drowsiness  is  indicated  by  drooping  of  the  eyelids;  hun- 
ger, by  uneasiness  in  the  stomach;  thirst,  by  dryness  of  the 
mouth  and  fauces;  and  the  "  besoin  de  respirer  "  and  sense 
of  suffocation,  when  respiration  is  interfered  with,  is  re- 
ferred to  the  lungs.  But  the  sensation  of  hunger  does  not 
reside  in  the  stomach,  though  it  may  be  momentarily  ar- 
rested by  the  introduction  of  substances,  even  of  an  indi- 
gestible character,  into  its  cavity.  In  a  patient  suffering 
from  any  disease  which  is  characterized  by  deficient  diges- 
tion and  assimilation,  while  the  system  is  capable  of  feeling 
the  want  of  nourishment,  an  abnormal  appetite  is  a  char- 
acteristic symptom;  and  the  hunger  is  not  appeased  for  any 
length  of  time  by  the  introduction  of  food  into  the  stom- 
ach. This,  as  is  well  known  to  practical  physicians,  is  a 
frequent  symptom  of  diabetes  and  chronic  diarrhoea.  Di- 
rect experiments  have  been  made  upon  the  sensation  of 
thirst.  Magendie  and  Bernard  kept  horses  without  water 
for  twenty-four  or  forty-eight  hours,  divided  the  oesopha- 
gus so  as  to  divert  food  and  water  from  the  stomach,  and 
then  allowed  them  to  drink.  As  fast  as  the  water  was  swal- 
lowed it  flowed  out  at  the  wound;  and  though  the  mouth 
and  fauces  were  moistened,  the  thirst  was  not  satisfied  and 
the  animals  continued  to  drink.  Bernard  has  made  similar 
experiments  on  dogs  in  which  he  had  established  gastric 


io6    ACTION    OF    THE    HEART    AND    RESPIRATION 

fistula}.  These  experiments  1  have  frequently  repeated, 
and  as  they  are  very  striking  and  easy  of  execution,  I  re- 
port an  example: 

Experiment  XXXV.  November  17,  i860. — A  dog  that  had 
been  operated  upon  for  the  establishment  of  a  gastric  fistula  two 
days  before  was  kept  without  water  for  twenty-four  hours.  At  the 
time  of  the  experiment  he  was  quite  lively,  having  suffered  little 
from  the  operation.  The  cork  was  then  removed  from  the  tube  in 
the  stomach  and  the  animal  was  allowed  to  drink.  He  drank  until 
he  desisted  from  actual  fatigue,  and  after  resting  for  a  moment 
drank  again  in  the  same  way,  the  fluid  all  this  time  flowing  freely 
from  the  fistula.  This  was  repeated  several  times  until  the  animal 
gave  up  the  effort.  The  cork  was  then  replaced  in  the  tube,  and 
when  the  animal  drank  his  thirst  was  soon  satisfied. 

These  experiments,  which  are  well  known  to  physiolo- 
gists, show  that  thirst  is  a  sensation  felt  in  the  tissues  but 
referred  to  the  mouth  and  fauces;  and  although  these  parts 
and  the  walls  of  the  stomach  may  be  continually  moistened, 
the  thirst  is  not  appeased,  nor  can  it  be  until  the  fluid  has 
been  taken  into  the  blood-vessels  and  circulates  in  the  sys- 
tem. This  desire  for  liquids  is  always  shown  by  animals 
after  the  withdrawal  of  blood.  I  have  repeatedly  observed 
animals  from  which  I  had  removed  blood  by  the  jugulars 
go  to  the  water  and  drink  copiously  so  soon  as  they  were 
set  at  liberty. 

Conclusions. — Respiration  is  a  reflex  phenomenon 
under  ordinary  conditions;  and  movements  connected 
with  it  are  due  to  an  impression  conveyed  from  the  general 
system  to  the  medulla  oblongata,  whence  a  stimulus  is  sent 
out  which  animates  the  inspiratory  muscles.  While  res- 
piration is  carried  on  efifectually  without  exertion  on  the 
part  of  an  animal,  as  in  artificial  respiration,  evidently 
no  impression  is  made  upon  the  respiratory  centre,  for  no 
respiratory  movements  take  place. 

The  impression  which  excites  respiratory  movements 
is  received  from  the  tissues  and  not  from  the  lungs;  for  it 
is  only  when  dark  blood  instead  of  red  is  supplied  to  the 
tissues,  that  the  impression  is  conveyed  to  the  respiratory 
centre,  producing  eiTorts  at  respiration. 

This  impression  is  not  transmitted  through  the  pneu- 
mogastric  nerves  but  through  the  general  sensory  nerves; 
for  there  is  no  difference  in  the  manifestation  of  respira- 


ACTION    OF    THE    HEART    AND    RESPIRATION    107 

tory  movements  when  the  supply  of  air  to  the  hmgs  is  cut 
off,  if  both  pneumogastrics  are  divided. 

This  impression  is  due  to  the  want  of  oxygen  in  the 
tissues  and  not  to  stimulating  properties  of  the  venous 
blood;  for  when  the  supply  of  oxygen  is  cut  off  by  abstract- 
ing blood  from  the  system,  the  phenomena  observed  as 
occurring  during  interruption  of  respiration  are  marked, 
though  air  is  supplied  in  abundance  to  the  lungs. 

This  impression  is  not  due  to  distension  of  the  cavities 
of  the  heart,  as  suggested  by  Berard;  because  the  heart 
may  be  removed  from  the  body  of  a  living  animal  and  the 
respiratory  efforts  will  occur  as  in  the  case  of  abstraction 
of  blood. 

This  impression  (the  sense  of  want  of  air,  "  besoin  de 
respirer  ")  when  exaggerated  constitutes  the  sense  of  suffo- 
cation; and  it,  like  the  sense  of  fatigue,  of  hunger  or  of 
thirst,  has  its  usual  source  in  the  general  system,  though  it 
manifests  itself  in  the  lungs  in  the  same  way  that  fatigue 
affects  the  eyelids,  hunger  the  stomach,  and  thirst  the 
mouth  and  fauces.  They  are  all  indications  of  wants  of 
the  system  and  can  not  be  effectually  relieved  by  the  local 
effects  of  anything  upon  the  organs  to  which  they  are  re- 
ferred by  the  sensations. 

The  necessity  for  respiration,  or  for  oxygen,  then,  ex- 
ists in  the  tissues;  and  asphyxia  can  not  be  solely  applied 
to  arrest  of  the  function  of  the  lungs,  but  to  anything  which 
interferes  with  the  consumption  of  oxygen  by  the  system. 
Anything  which  operates  in  this  way  gives  rise  to  a  sense 
of  suffocation  and  afterward  to  general  convulsions  if  it 
is  carried  sufficiently  far.  Various  pathological  phenome- 
na which  would  otherwise  be  obscure  are  thus  explained. 
The  operation  of  simple  asphyxia  by  tying  the  trachea  or 
preventing  air  from  gaining  entrance  into  the  lungs  in- 
duces the  sense  of  suffocation  which  first  gives  rise  to  re- 
spiratory efforts  more  violent  than  ordinary,  and  subse- 
quently, to  general  convulsions.  All  are  familiar  with 
these  phenomena  however  they  may  be  explained. 

In  poisoning  by  carbonic  oxide  there  are  general  con- 
vulsions which  arise  from  the  sense  of  suffocation;  for  this 
agent  so  operates  upon  the  blood-corpuscles,  that  though 
they  continue  red  they  are  rendered  incapable  of  perform- 
ing their  function  of  supplying  oxygen  to  the  system. 


io8   ACTION    OF   THE    HEART   AND    RESPIRATION 

In  poisoning  by  hydrocyanic  acid,  when  the  system 
is  not  immediately  overpowered  by  this  agent  and  the  mus- 
cular irritability  destroyed,  the  blood  becomes  incapable 
of  supplying  oxygen  to  the  system  and  convulsions  ensue 
as  the  result  of  the  sense  of  suffocation. 

In  death  by  hemorrhage,  convulsions,  occurring  just 
before  death,  are  invariable.  This  also  is  the  result  of  de- 
ficient supply  of  oxygen  to  the  tissues,  and  the  sense  of 
suffocation  is  the  starting  point.  This  was  demonstrated 
in  Experiment  XXXIV.,  in  which  the  animal  was  bled  to 
death.* 

Finally,  in  all  cases  where  the  supply  of  oxygen  is  cut 
ofT,  not  from  the  lungs  but  from  the  tissues,  a  sense  of 
suffocation  is  the  result,  and  convulsions  ensue  following 
violent  efforts  at  respiration. 

Summary. — In  the  foregoing  essay,  I  think  I  have 
established  the  following  facts,  which  are  either  not  gen- 
erally admitted  or  not  vmderstood  by  physiologists: 

I.  That  the  heart  elongates  during  the  systole  of  its 
ventricles. f 

II.  That  the  cause  of  the  rhythmical  contraction  of  the 
muscular  fibres  of  the  heart  is  resident  in  the  fibres  them- 
selves, is  one  of  their  inherent  properties  and  remains  so 
long  as  they  retain  their  "  irritability." 

III.  That  the  normal  stimulus  which  excites  the  regu- 
lar and  efficient  movements  of  the  heart  is  the  blood,  and 
that  this  can  not  be  replaced  by  a  fluid  of  less  density. 

IV.  That  although  the  flow  of  blood  m  the  cavities  of 
the  heart  is  sufficient  to  induce,  under  ordinary  conditions, 
regular  contractions  of  the  organ,  still  it  is  necessary  that 
these  movements  be  further  regulated  and  controlled;  and 
that  this  is  effected  mainly  through  the  agency  of  the  pneu- 
mogastric  nerves. 

V.  That  the  action  of  the  heart  may  be  arrested 
through  the  motor  filaments  of  the  pneumogastric  nerves 
by  means  of  electricity:  that  this  does  not  take  place  in 
animals  poisoned  by  curara.  on  account  of  the  paralysis  of 
the  motor  nerves.     That  the  motor  filaments  of  the  pneu- 

*  These  convulsions  have  been  explained  in  various  ways  by  physiologists 
but  never  satisfactorily,  though  they  have  long  been  observed. 
f  See  foot-note  on  page  69. 


ACTION    OF   THE    HEART    AND    RESPIRATION    109 

mogastrics  are  the  last  which  are  affected  by  this  agent, 
and  that  in  the  aUigator  they  are  left  almost  intact.  That 
the  cause  of  the  arrest  of  the  heart's  action  by  stimulation 
of  the  pneumogastrics  is  an  exaggeration  of  the  force  which 
regulates  the  action  of  the  heart,  rendering  it  slower  and 
more  powerful. 

VI.  That  in  asphyxia,  the  cause  of  the  arrest  of  the 
action  of  the  heart  is  overdistension  of  its  cavities;  and 
that  anything  which  brings  about  sufficient  distension  will 
also  arrest  the  action  of  this  organ. 

VII.  That  the  auriculo-ventricular  valves  are  closed 
by  a  backward  pressure  operating  during  the  contraction 
of  the  ventricles,  and  not  by  the  current  of  blood  from  the 
auricles  to  the  ventricles. 

VIII.  That  the  impression  which  gives  rise  to  the  re- 
flex acts  of  respiration  is  received  from  the  general  system 
and  not  from  the  lungs  or  heart.  That  this  impression  is 
due  to  the  want  of  oxygen  in  the  tissues  and  not  to  stimu- 
lating properties  of  the  venous  blood.  That  the  exaggera- 
tion of  this  impression  constitutes  the  sense  of  suffocation 
and  gives  rise,  if  excessive,  to  general  convulsions. 


APPENDIX 

Some  Points  in  the  Anatomy  of  the  Circulatory 
System  of  the  Crocodilus  Mississippiensis,  or  Alli- 
gator.— The  anatomy  of  the  alligator  is  imperfectly  and  in 
many  respects  incorrectly  described  in  most  works  upon 
Natural  History.  The  description  of  the  circulatory  appa- 
ratus, however,  given  by  Milne  Edwards,*  in  his  work  on 
"  Physiology  and  the  Comparative  Anatomy  of  Man  and 
the  Inferior  Animals,"  now  in  course  of  publication,  is  quite 
accurate;  and  as  the  arrangement  of  the  heart  and  larger 
vessels  is  peculiar,  I  have  thought  that  a  sketch  of  these 
parts  might  not  be  uninteresting. 

The  heart  is  quite  small  in  proportion  to  the  size  of  the 
animal,  and  like  the  organ  in  reptiles  generally,  the  ven- 
tricular portion  is  small  in  proportion  to  the  size  of  the 
auricles.     The  position,  shape,  etc.,  of  the  auricles  do  not 

*  For  a  full  description  of  the  circulatory  system  of  the  alligator,  see  Milne 
Edwards,  "  Le9ons  sur  la  physiologic,"  etc.,  tome  iii.,  p.  424  et  seq. 


no   ACTION   OF   THE    HEART   AND   RESPIRATION 

differ  from  those  in  other  reptiles,  except  that  the  right 
auricle  is  much  larger  than  the  left;  but  the  ventricular 
portion  is  divided  by  a  complete  septum  into  two  chambers, 
a  right  and  a  left,  like  the  heart  of  a  warm-blooded  animal. 
From  the  ventricles  arise  the  two  aortie;  one  from  the 
left,  and  one  from  the  right  side.  There  is  also  a  pulmo- 
nary artery  going  to  the  lungs  from  the  right  ventricle. 
The  right  aorta  passes  immediately  over  to  the  left  side; 
and  as  it  carries  venous  blood,  it  may  be  called  the  venous 
aorta;  while  the  left,  or  arterial  aorta,  passes  directly  over 
to  the  right  side.  There  is  no  communication  betw^een 
either  auricles  or  ventricles  upon  the  two  sides;  but  at  the 
origin  of  the  two  aortre  is  an  opening  which  permits  a  mix- 
ture of  venous  and  arterial  l)lood  to  a  limited  extent.  This 
is  called  the  foramen  of  Pinazza,  because  its  discovery  w^as 
formerly  supposed  to  belong  to  him.  It  was  described 
by  Hentz,  an  American  anatomist,  in  1824,  in  a  paper  pub- 
lished in  the  "  Transactions  of  the  American  Philosophical 
Society,"  while  Pinazza  described  it  in  1833.  Following 
out  now^  the  distribution,  etc.,  of  these  tw'o  aortse,  the  arte- 
rial aorta  first  gives  off  a  large  branch,  the  brachio-cephalic, 
which  almost  immediately  gives  off  the  left  subclavian 
going  to  the  left  superior  extremity.  The  brachio-cephalic 
divides  into  the  left  subclavian,  already  mentioned,  and  a 
single  carotid  artery  which  goes  in  the  median  line  to  the 
base  of  the  skull,  there  divides  into  two  vessels,  which  soon 
bifurcate  and  form  the  external  and  internal  carotids  of 
the  two  sides,  the  internal  going  to  the  encephalon,  and 
the  external  to  the  muscles,  etc.,  about  the  head.  Next 
is  given  off  the  right  subclavian  artery,  distributed  to  the 
right  superior  extremity.  Each  subclavian  artery,  a  short 
distance  from  its  origin,  gives  off  a  small  cervical  artery, 
which  goes  to  the  head  and  is  accompanied  by  the  jugular 
vein  and  the  pneumogastric  nerve.  These  are  the  princi- 
pal branches  which  are  given  off  by  the  arterial  aorta  alone. 
The  venous  aorta  gives  off  no  branches  in  the  neck,  but 
passes  back  to  the  vertebral  column,  anastomoses  by  a 
branch  of  considerable  size  with  the  arterial  aorta,  and 
sends  a  branch,  larger  even  than  the  anastomosing  branch, 
to  some  of  the  abdominal  viscera,  which  are  thus  supplied 
with  venous  blood.  The  dorsal  aorta  is  formed  by  the 
union  of  the  arterial  aorta  with  the  anastomosing  branch 


ACTION    OF    THE    HEART    AND    RESPIRATION    in 

of  the  venous  aorta,  and  thus  carries  mixed  blood.  It 
passes  down  the  back,  gives  off  in  its  course  the  inter- 
costals,  the  anterior  mesenteric,  the  renal  arteries,  the  ves- 
sels of  the  posterior  limbs,  the  posterior  mesenteric  and 
finally  is  distributed  to  the  tail. 

The  distribution  of  the  blood  in  this  animal  is  peculiar. 
The  forelegs,  the  head  and  face  are  supplied  with  almost 
pure  arterial  blood,  as  the  communication  by  the  foramen 
of  Pinazza  is  very  imperfect.  There  is  but  a  single  carotid 
artery  in  the  neck,  and  the  pneumogastric  nerves  are  found 
accompanying  the  cervical  arteries,  w'hich  are  given  off 
by  the  subclavians.  Some  of  the  abdominal  viscera,  the 
stomach,  liver,  spleen,  etc.,  are  supplied  with  venous  blood. 
The  kidneys,  intestines,  hind  legs  and  tail  are  supplied  wdth 
a  mixture  of  arterial  and  venous  blood.* 

The  length  of  time  for  which  the  nervous  and  muscular 
irritability  in  these  animals  is  retained  after  death  renders 
them  very  valuable  in  many  physiological  experiments.  I 
have  found  that  when  poisoned  with  curara  this  persisted 
for  days.  For  a  considerable  time,  four  or  five  days  after 
death,  even  when  the  weather  was  quite  warm,  no  decom- 
position took  place.  I  do  not  know  that  this  apparently 
antiseptic  property  of  curara  has  ever  been  remarked,  but 
it  certainly  seemed  to  retard  decomposition  in  the  alligators 
upon  which  I  have  experimented. 

*  The  description  of  the  heart  and  arteries,  which  is  here  given,  is  nearly 
if  not  precisely  according  to  the  views  entertained  by  Dr.  Bennett  Dowler,  of 
New  Orleans,  who  has  made  extensive  researches  into  the  anatomy  and  physi- 
ology of  the  alligator.  These  views,  however,  have  never  been  fully  published 
by  him  but  were  verbally  communicated  to  me. 


VI 

MECHANISM    OF   REFLEX    NERVOUS   ACTION 
IN  NORMAL   RESPIRATION 

AN    ADDRESS    DELIVERED    FEBRUARY    l6,    1 874,    BEFORE   THE   NEW 
YORK    SOCIETY    OF   NEUROLOGY   AND    ELECTROLOGY  * 

Published  in  the   "  Chicago  Journal  of  Nervous  and  Mental  Diseases  "  for 

April,  1874. 

Mr.  President,  and  Gentlemen  of  the  Society: 
I  shall  have  the  honor  this  evening  of  making  some  re- 
marks on  the  mechanism  of  nervous  reflex  action  in  nor- 
mal respiration.  A  great  part  of  the  statements  that  I  shall 
make  and  the  views  advanced  upon  this  subject  are  derived 
from  personal  experimentation;  but  they  are  not  entirely 
new,  for  many  of  the  experiments  upon  which  my  views 
are  based  were  published  in  the  ''  American  Journal  of 
Medical  Sciences,"  in  October,  1861.  Still,  these  experi- 
ments, which  seem  to  me  to  be  of  considerable  importance, 
have  been  noticed  so  Httle  in  physiological  writings  that  I 
venture  to  assume  that  they  may  be  new  to  many  of  those 
who  now  listen  to  me. 

After  Marshall  Hall  had  formularized  the  ideas  of  cer- 
tain of  his  predecessors  in  regard  to  what  he  termed  re- 
flex action,  it  was  pretty  generally  understood  by  physi- 
ologists that  the  movements  of  respiration  were  of  a  purely 
reflex  character,  unless  they  were  modified  by  voluntary 
acts;  and  that  the  ordinary  movements  of  respiration,  which 
take  place  without  the  intervention  of  the  will,  were  en- 
tirely reflex. 

The  experiments  that  I  shall  detail  this  evening  were 
based  upon,  or  rather  suggested  by  an  experiment  made 
in  1664,  by  the  celebrated  Robert  Hooke,  and  published 
in  the  "  Philosophical  Transactions  "  for  1667.  This  ex- 
periment, though  it  could  not  be  completely  understood 

*  Phonographically  reported  by  George  W.  Wells,  M.  D.,  of  New  York. 
112 


NERVOUS   ACTION    IN    RESPIRATION  113 

at  the  time  it  was  made,  in  1664,  is  very  instructive.  It 
consisted  in  introducing  a  bellows  into  the  trachea  of  a 
dog,  making  an  opening  into  the  chest,  cutting  off  a  por- 
tion of  the  lungs  and  forcing  air  through  them;  and  it  was 
found  that  so  long  as  air  was  forced  through  the  lungs  in 
this  way  the  animal,  though  sensible,  made  no  eft'orts  at 
respiration.  I  may  here  anticipate  enough  to  say  that  I 
shall  assume  that  in  this  experiment,  while  air  was  supplied 
to  the  system  the  animal  felt  no  want  of  it,  had  no  inclina- 
tion to  respire  and  consequently  did  not  respire. 

In  studying  the  subject  of  the  reflex  nervous  action  in 
respiration,  one  is  immediately  struck  with  the  anatomical 
relations  of  the  pneumogastric  nerves  to  the  respiratory 
apparatus;  and  it  is  all  the  more  important  to  study  the 
relations  of  these  nerves  to  the  process  of  respiration,  as 
they  arise  near  that  point  in  the  medulla  oblongata  where 
the  so-called  "  vital  knot,"  or  the  respiratory  nerve-cen- 
tre, is  supposed  to  be  situated. 

It  may  be  opportune,  perhaps,  to  rapidly  sketch  the 
■condition  of  knowledge  respecting  the  influence  of  the 
pneumogastric  nerve  upon  respiration. 

The  pneumogastric  nerve  is  one  of  immensely  wide 
■distribution  and  is  connected  with  various  distinct  func- 
tions. The  branches  that  are  distributed  to  the  respiratory 
■organs  are  the  follov/ing: 

The  superior  laryngeals,  which  are  distributed  to  the 
mucous  membrane  of  the  larynx  and  the  membrane  cover- 
ing the  top  of  the  larvnx,  sending  off  a  branch  on  either 
side  to  the  crico-thyroid  muscle,  this  branch  being  a  mixed 
nerve. 

Next  in  order  are  the  inferior,  or  recurrent  laryngeal 
nerves,  which  are  distributed  to  all  the  intrinsic  muscles  of 
the  larynx  except  the  crico-thyroid.  These  nerves  are 
composed  entirely  of  motor  filaments  and  are  derived  from 
a  variety  of  sources.  The  experiments  of  Bernard,  which 
have  been  so  often  repeated  by  Dr.  Dalton,  myself  and 
others,  of  extirpating  the  spinal  accessory  nerves,  or  the 
•section  of  the  communicating  branches  to  the  pneumogas- 
trics,  show  that  the  spinal  accessory  is  the  nerve  of  phona- 
tion;  and  the  filaments  that  preside  over  the  voice  pass 
to  the  larynx  through  the  recurrent  laryngeals. 

Then,  distributed  to  the  lungs  themselves,  are  the  an- 


114  NERVOUS    ACTION    IN    RESPIRATION 

terior  and  posterior  pulmonary  branches,  which  go  almost 
exclusively  to  the  mucous  membrane  of  the  pulmonary 
structure.  These  branches  communicate  with  the  sympa- 
thetic; but  according  to  Sappey,  they  do  not  go  to  the 
walls  of  the  blood-vessels,  being  distributed  to  the  mem- 
brane of  the  bronchia  and  the  air-vesicles. 

So  much  for  the  distribution,  in  general  terms,  of  those 
branches  of  the  pneumogastrics  which  go  to  the  lungs;  and 
this  distribution  being  so  extensive,  one  can  hardly  discuss 
the  reflex  nervous  action  in  respiration  without  taking  the 
action  of  these  nerves  into  consideration. 

The  pneumogastric  is  originally  an  exclusively  sensory 
nerve.  Experiments  are  somewhat  ol)scure  upon  this. 
point,  on  account  of  the  difficulty  in  irritating  the  original 
roots  of  the  pneumogastrics  without  involving  filaments 
of  other  nerves;  still,  the  careful  experiments  of  Longet 
showed  that  when  the  spinal  cord  of  animals  is  opened  and 
the  roots  of  the  pneumogastrics  are  carefully  isolated  and 
stimulated,  no  movements  follow  their  irritation.  This 
shows  that  the  original  filaments  of  the  pneumogastric  are 
not  motor;  but  as  the  nerve  emerges  from  the  cranial  cav- 
ity, it  receives  a  number  of  communicating  motor  fila- 
ments, and  thus  in  its  course  it  is  a  mixed  nerve.  Follow- 
ing out  the  distribution  to  the  respiratory  apparatus,  it  is 
found  that  the  filaments  from  the  superior  laryngeal  going 
to  the  crico-thyroid  muscle  are  almost  exclusively  motor; 
the  motor  filaments  of  the  recurrents  go  to  the  intrinsic 
muscles  of  the  larynx,  whereas  the  true  pulmonary  branches 
are  distributed  to  the  mucous  membrane.  Therefore,  ex- 
cluding the  movements  of  the  larynx,  the  action  of  the 
pneumogastric  in  the  reflex  phenomena  of  respiration,  the- 
oretically, would  be  that  of  a  sensory  nerve,  conveying  to 
the  respiratory  nervous  centre  an  impression,  or  sensation^ 
which  gives  rise  to  the  movements  of  respiration. 

If  both  pneumogastrics,  however,  are  divided,  the  re- 
spiratory movements  are  very  much  diminished  in  frequen- 
cy; and  I  have  in  my  mind  an  experiment  in  which  they 
were  reduced  from  twenty-four  to  four  or  six  in  a  minute;, 
yet  they  still  continue;  and  this  simple  experiment,  so  often 
performed  as  a  class-demonstration,  is  a  denial  of  the  propo- 
sition that  the  pneumogastrics  are  the  only  nerves  for  the 
transmission  of  the  so-called  "  besoin  de  respirer,"  or  sense 


NERVOUS    ACTION    IN    RESPIRATION  115 

of  want  of  air,  to  the  respiratory  nerve-centre.  If  the  pneii- 
mogastrics  were  the  only  nerves  having  this  function,  res- 
piration should  cease  after  their  division;  but  it  does  not. 

I  think  that  physiologists  are  not  at  present  able  to 
explain  the  cause  of  the  great  diminution  in  frequency  of 
the  respiratory  movements  after  the  division  of  both  pneu- 
mogastric  nerves;  but  this  is,  nevertheless,  an  invariable 
phenomenon.  In  the  experiment  to  which  I  have  referred, 
curiously  enough  the  animal  did  not  die;  and  when  I  pre- 
sented him  to  my  class,  about  three  weeks  after  the  section 
of  the  nerves,  the  number  of  respirations  had  returned  to 
the  normal  standard.  I  imagine  that  a  reunion  of  the  two 
ends  of  the  divided  nerve  had  occurred.  A  post-mortem 
examination,  the  animal  being  sacrificed  in  another  ex- 
periment, showed  that  the  nerves,  though  not,  perhaps, 
completely  united,  had  formed  a  partial  union  between  the 
divided  extremities. 

The  condition  of  the  lungs  after  division  of  the  pneu- 
mogastrics — that  is,  in  cases  where  death  follows  such 
division — is  peculiar  and  was  for  a  long  time  unexplained 
by  physiologists.  In  animals  that  live  for  three  or  four 
days  and  then  die,  the  lungs  present  pretty  generally, 
throughout  their  entire  substance,  a  carnified  condition. 
They  are  solid,  will  sink  in  water,  but  still  do  not  present 
evidences  of  inflammation.  It  was  thought  at  first  that 
this  was  due  to  inflammation;  but  physiologists  failed  to 
find  the  positive  evidence  of  any  such  process.  Bernard, 
I  think,  has  given  the  correct  explanation  of  this  peculiar 
appearance.  He  observed  that  when  the  respiratory  move- 
ments are  gradually  diminished  in  frequency  they  are  im- 
mensely increased  in  depth ;  that  the  in.gpirations  are  re- 
markably prolonged  and  profound;  and  that  the  chest,  in 
the  inspiratory  act,  is  extraordinarily  distended.  He  ad- 
vanced the  idea  that  this  extreme  dilatation  of  the  air-cells 
induced  capillary  haemorrhage  in  certain  parts  of  the  lungs; 
that  as  this  extended,  the  blood  coagulated;  and  finally, 
the  lungs  became  almost  solid. 

Faradization  of  both  pneumogastrics  in  the  neck  ar- 
rests the  respiratory  movements,  if  it  is  powerful;  and  this 
action  is  reflex,  not  direct.  If  the  nen-es  are  divided,  fara- 
dization of  their  peripheral  extremities  has  no  effect  on 
respiration,  though  it  arrests  the  action  of  the  heart;  where- 


ii6  NERVOUS   ACTION    IN   RESPIRATION 

as  faradization  of  the  central  ends  arrests  respiration  in  the 
same  way  as  faradization  of  the  nerves  before  their  division. 
FaracHzation  of  the  superior  laryngeal  nerves  arrests  respi- 
ration and  renders  the  animal  motionless.  This  effect  fol- 
lows powerful  faradization  of  any  of  the  sensitive  nerves, 
though  not  so  certainly  and  promptly  as  faradization  of  the 
superior  laryngeals.  If  the  superior  laryngeals  are  power- 
fullv  stimulated,  respiration  stops  immediately  and  is  ar- 
rested at  the  instant  the  current  is  applied,  but  more  easily 
during  inspiration  than  expiration.  This  arrest  of  the 
respiratory  movements  is  particularly  marked  as  regards 
the  action  of  the  diaphragm.  I  have  made  these  prelimi- 
nary remarks  to  show  that  there  is  very  little  known  in 
regard  to  the  reflex  phenomena  of  respiration  operating 
through  the  pneumogastrics. 

Although  the  proposition  that  I  am  about  to  make  has 
been  denied  by  a  few  physiologists,  still,  the  greater  num- 
ber believe  that  the  medulla  oblongata  is  the  respiratory 
nerve-centre.  Adopting  this  view%  which  is  almost  univer- 
sally accepted,  the  mechanism  of  the  reflex  phenomena  of 
respiration  may  be  briefly  stated  as  follows: 

These  phenomena  require  three  conditions: 

I.  The  physiological  integrity  of  nervous  filaments  con- 
veying a  certain  impression,  or  sense,  to  the  nerve-centre. 

II.  The  existence  and  physiological  integrity  of  the 
nerve-centre. 

III.  Finally,  the  physiological  integrity  of  the  motor 
nerves  which  convey  the  stimulus  that  is  generated  at  this 
nerve-centre  to  the  inspiratory  muscles. 

If  it  be  assumed  that  respiration  involves  a  reflex  ac- 
tion, it  must  be  admitted  that  there  are  nerves  which  con- 
vey certain  impressions  to  the  medulla  oblongata.  The 
medulla  oblongata  is  the  respiratory  centre:  and  when  this 
centre  is  destroyed,  the  movements  of  inspiration  instantly 
and  permanently  cease.  A  single  series  of  experiments  has 
been  published  by  Dr.  Brown-Sequard,  which  are  assumed 
to  prove  that  respiratory  movements  may  occasionally  per- 
sist after  destruction  of  the  medulla  oblongata;  but  they 
have  never  been  confirmed  and  can  not  be  accepted  as 
demonstrating  that  the  medulla  oblongata  is  not  the  cen- 
tre for  respiration. 

The  sensation  of  want  of  air  has  been  called  by  the 


NERVOUS   ACTION    IN    RESPIRATION  117 

French,  the  "  besoin  de  respirer."  It  might  be  well  enough 
to  call  it,  indeed,  the  sense  of  the  want  of  air.  Under 
ordinary  conditions,  when  respiration  is  free  and  when 
the  surrounding  air  is  pure  and  in  abundance,  this  sensation 
is  not  felt  except  at  the  medulla  oblongata.  This  impres- 
sion, however,  at  proper  intervals  is  conveyed  to  the  me- 
dulla and  keeps  up  the  respiratory  movements,  without  our 
knowledge;  and  it  is  only  when  there  is  a  greater  deficiency 
of  air  than  usual  or  when  there  is  an  obstruction  to  respi- 
ration, that  this  sense  of  want  of  air  becomes  a  positive 
sensation,  in  the  form  of  a  sense  of  suffocation,  more  or 
less  pronounced.  I  think  that  the  old  experiment  of  Rob- 
ert Hooke  established  this  point;  and  it  certainly  demon- 
strates it,  when  taken  in  connection  with  what  has  been 
learned  of  late  years. 

In  Robert  Hooke's  experiment  the  dog  was  supplied 
artificially  with  air,  completely  and  efficiently;  and  it  was 
noted  that  so  long  as  the  respiratory  needs  were  supplied, 
though  the  animal  looked  around  and  was  entirely  sensible, 
he  made  no  respiratory  efforts.  This  showed  that  during 
the  free  passage  of  air  through  the  lungs  the  want  of  air 
was  not  felt  by  the  medulla  oblongata  and  there  was  no 
stimulus  to  induce  respiratory  movements.  There  was 
no  necessity  felt  for  respiratory  movements  and  none  took 
place.  This  experiment  suggested  my  own  observations 
made  in  186 1.  I  put  an  animal,  a  dog,  completely  under 
the  influence  of  ether,  introduced  the  nozzle  of  a  bellows 
into  the  trachea,  opened  the  chest,  turned  back  the  an- 
terior walls  by  breaking  the  ribs,  so  that  I  exposed  the 
lungs  and  diaphragm,  and  then  very  carefully  maintained 
artificial  respiration.  I  found  that  while  artificial  respira- 
tion was  complete  and  efficient  the  animal  remained  per- 
fectly quiet  and  made  no  respiratory  efforts.  I  could  see 
in  this  experiment  the  slightest  movement  of  the  dia- 
phragm. I  then  interrupted  the  artificial  respiration  for 
a  moment.  Very  soon  I  could  see  the  diaphragm  begin 
to  quiver;  it  contracted  at  first  slightly;  then,  more  and 
more  powerfully  and  rhythmically;  and  the  animal  finally 
opened  the  mouth  and  made  ineffectual  efforts  to  breathe. 
I  then  resumed  the  artificial  respiration,  and  in  a  short 
time,  when  the  respiratory  needs  were  entirely  supplied, 
the  animal  became  quiet. 


ii8  NERVOUS    ACTION    IN    RESPIRATION 

I  then  exposed  an  artery  and  introduced  in  it  a  stop- 
cock, so  that  I  could  take  blood  from  the  vessel  at  will. 
While  I  kept  up  artificial  respiration,  1  drew  a  little  blood 
from  the  artery  upon  a  white  plate.  It  had  all  the  charac- 
ters of  pure  arterial  blood.  1  then  had  my  assistant,  who 
was  workini^  the  bellows,  stop  the  artificial  respiration  and 
I  allowed  the  blood  to  flow  in  a  small  stream  from  the  ar- 
tery. I  found,  always  and  invariably,  that  when  the  blood 
began  to  be  dark  in  the  artery,  and  not  before,  the  animal 
made  efforts  to  respire. 

There  are  several  views,  which  have  l)een  advanced  by 
physiologists  from  time  to  time,  as  to  the  location  of  the 
"  besoin  de  respirer." 

Marshall  Hall  and  some  others  thought  that  it  was  due 
to  a  want  of  air  in  the  lungs  themselves,  and  that  this 
want  was  conveyed  by  the  pneumogastric  nerves  to  the 
medulla  oblongata;  but  I  do  not  see  how,  under  this  sup- 
position, it  is  possible  to  explain  respiratory  movements 
which  occur  after  division  of  both  pneumogastrics. 

Reid  thought  that  the  sense  of  want  of  air  w-as  due  to 
the  circulation  of  venous  blood  in  the  medulla  oblongata. 

Berard  thought  that  the  sense  of  want  of  air,  or  the 
"  besoin  de  respirer,"  was  due  to  the  distension  of  the  left 
side  of  the  heart  by  venous  blood  when  respiration  was 
arrested.  In  support  of  this  view,  he  brought  forward  the 
well-known  fact  that  in  certain  cases  of  disease  of  the  heart, 
even  when  the  lungs  are  perfectly  normal  and  completely 
filled  with  air,  there  is  frequently  a  sense  of  suffocation. 

Vierordt  thought  that  the  sense  of  want  of  air  was 
due  to  the  circulation  of  venous  blood  in  the  substance  of 
the  nerves  themselves. 

Volkmann,  in  1842,  made  the  very  important  observa- 
tion that  an  animal  experiences  the  sense  of  suffocation 
when  deprived  of  air  after  division  of  both  pneumogastrics. 
This  fact  was  well  known.  Every  one  who  has  divided 
both  pneumogastric  nerves  in  a  cat  must  have  noted  that 
the  animal  experiences  intense  distress  from  suffocation. 
In  this  animal  the  cartilages  of  the  larynx  are  very  flexi- 
ble, and  paralysis  of  both  recurrent  laryngeal  nerves,  which 
follows  division  of  the  pneumogastrics  in  the  neck,  causes 
the  glottis  to  close  in  inspiration,  so  that  the  animal  is 
almost  immediately  deprived  of  air.     Volkmann  reasoned 


NERVOUS    ACTION    IN    RESPIRATION  119 

from  this  fact,  which  had  often  been  observed  before,  that 
the  sense  of  want  of  air  resides  in  the  general  system  and 
is  not  to  be  referred  to  any  particular  organ  or  organs. 

If  I  may  be  permitted,  now,  to  continue  the  account 
of  my  own  experiments,  I  think  I  can  show  that  it  is  cer- 
tain that  the  sense  of  want  of  air  resides  in  the  general  sys- 
tem; and  furthermore,  that  it  is  due  to  a  want  of  oxygen 
in  the  general  system. 

Here  is  an  animal  with  the  heart  and  lungs  exposed; 
a  bellows  placed  in  the  trachea,  and  artificial  respiration 
maintained;  but  there  are  no  efforts  at  breathing  so  long 
as  air  is  supplied  in  sufficient  quantity.  Put  a  stop-cock 
in  the  artery,  and  while  artificial  respiration  is  continued, 
there  is  the  natural  red  color  to  the  blood.  Stop  the  respi- 
ration, however,  and  just  so  soon,  and  no  sooner,  as  the 
blood  becomes  markedly  dark  in  the  arteries,  the  animal 
begins  to  make  efforts  at  respiration  and  feels  the  sense 
of  want  of  air.  I  think  this  experiment  shows  that  the 
sense  of  want  of  air  is  due  to  the  circulation  in  the  system 
of  blood  more  or  less  venous  in  its  character. 

\\niat  is  the  cause  of  this  sense  of  want  of  air  and  what 
are  the  conditions  of  the  blood  that  are  different  from  the 
conditions  during  efficient  artificial  respiration!  Of  course, 
w^hatever  they  may  be,  these  two  conditions  are  present: 
one,  a  deficiency  of  oxygen  in  the  blood  that  is  rendered 
more  or  less  venous;  and  another,  the  presence  in  the  ar- 
teries of  blood  containing  an  excess  of  carbonic  acid.  The 
question  now  arises,  whether  the  sense  of  want  of  air  is 
due  to  a  deficiency  of  oxygen  in  the  system  or  to  the  irri- 
tating qualities  of  carbonic  acid.  How  can  these  two  con- 
ditions be  separated  experimentally;  and  how  can  the 
tissues  be  deprived  of  oxygen  without  supplying  blood 
charged  with  carbonic  acid!  A  very  simple  way  is  to  drain 
the  system  of  blood;  for  if  blood  gets  to  the  system,  there 
is  no  question  that  oxygen  will  be  carried  to  the  tissues, 
it  being  always  conveyed  l^y  the  blood,  and  by  the  blood 
alone.  Therefore,  if  the  system  is  deprived  of  blood  no 
oxygen  can  get  to  the  tissues.  Again,  if  the  system  is 
drained  of  blood  by  cutting  out  the  heart,  the  question 
whether  or  not  the  sense  of  want  of  air  is  due  to  the  dis- 
tension of  the  left  side  of  the  heart  by  venous  blood  is 
answered.     Take  this  same  animal,  that  is  not  breathing, 


120  NERVOUS   ACTION   IN    RESPIRATION 

the  respiration  being  kept  up  by  the  bellows,  and  tie  a 
ligature  around  the  aorta;  he  begins  to  breathe,  although 
the  lungs  are  supplied  with  air,  for  the  reason  that  the  oxy- 
gen-carrying blood  is  cut  off  from  the  system.  If,  now,  in 
this  same  animal,  the  heart  is  suddenly  cut  out,  the  sys- 
tem is  of  course  almost  instantly  drained  of  blood;  and  the 
animal  always  makes  violent  and  repeated  respiratory  ef- 
forts, although  the  lungs  are  fully  supplied  with  air.  It 
seems  to  me  that  these  experiments  show  conclusively 
that  the  sense  of  want  of  air  is  derived  from  the  general 
system;  that  it  is  due  to  a  w-ant  of  oxygen  in  the  system, 
and  not  to  the  irritating  properties  of  carbonic  acid;  and 
that  this  sense  is  entirely  analogous  to  the  sense  of  hunger 
and  the  sense  of  thirst.  The  sensations  of  hunger  and  of 
thirst  are  subjectively  referred  to  the  stomach  or  to  the 
mouth  and  fauces;  but  they  really  reside  in  the  general 
system.  If  a  fistula  is  made  in  the  stomach  of  a  dog,  and 
if  the  animal  is  allowed  to  drink,  after  having  been  de- 
prived of  water  for  a  day  or  two,  the  water  will  flow  out 
through  the  fistula  as  fast  as  it  is  taken  into  the  stomach; 
and  although  the  animal  will  continue  to  drink,  the  water 
is  not  absorbed  and  the  thirst  is  not  satisfied.  I  have  seen 
animals  drink,  in  this  way,  gallons  of  water,  being  satisfied 
with  a  moderate  quantity  after  the  fistula  has  been  closed. 
Also,  *if  food  is  taken  into  the  stomach  and  not  absorbed, 
the  sense  of  hunger  is  but  momentarily  appeased;  but 
this  sense  is  referred  to  the  stomach  because  food  is  nat- 
urally introduced  into  the  system  by  the  stomach.  So  the 
sense  of  want  of  air.  which  I  believe  to  be  due  to  the  w'ant 
of  oxygen  in  the  tissues,  is  referred  to  the  respiratory  or- 
gans because  it  is  by  filling  the  thorax  that  this  deficiency 
in  the  system  is  naturally  supplied.  If  the  sense  of  w^ant 
of  air  becomes  exaggerated,  it  constitutes  the  sense  of 
suffocation;  and  this  is  one  of  the  most  distressing  of  sen- 
sations. 

It  has  been  observed  that  convulsions  ver\^  often  follow 
hemorrhage;  and  this  fact  has  been  found  difificult  of  ex- 
planation. But  hemorrhage  is  really  suffocation;  and  con- 
vulsions are  generally  observed  in  suffocation.  It  makes 
very  little  difference,  practically,  whether  the  system  is 
drained  of  the  oxygen-carrying  fluid  or  whether  oxygen 
is  prevented  from  going  to  the  lungs;  in  either  case  the 


NERVOUS    ACTION    IN    RESPIRATION  121 

same  result  follows  as  far  as  respiration  is  concerned;  and 
in  death  from  profuse  or  sudden  hemorrhage,  it  seems  to 
me  that  the  convulsions  are  in  fact  no  more  than  convul- 
sions due  to  suffocation.  This  view  seems  to  offer  a  satis- 
factory explanation  of  the  convulsions  following  hemor- 
rhage. There  is  one  point,  however,  in  this  connection, 
which  is  interesting  and  which  I  appreciate  as  fully  as  any 
one  who  now  hears  me. 

I  have  assumed  that  draining  the  system  of  blood,  by 
preventing  the  oxygen  from  getting  to  the  system  without 
carrying  to  the  tissues  carbonic  acid,  proves  that  the  sense 
of  the  want  of  air  is  due  to  a  want  of  oxygen  in  the  tissues 
and  not  to  the  stimulation  of  carbonic  acid.  Carbonic  acid 
does  not  originate  in  the  blood,  and  it  is  undoubtedly  an 
excretion.  A  muscle  cut  from  a  living  frog  and  put  under 
a  bell-glass  containing  oxygen,  even  though  it  contains  no 
blood,  will  respire.  Again,  the  same  muscle  in  an  atmos- 
phere of  hydrogen  will  give  off  a  certain  quantity  of  car- 
bonic acid.  In  normal  nutrition  carbonic  acid  is  carried 
away  from  the  tissues,  almost  as  soon  as  it  is  formed,  by 
the  blood.  If,  then,  the  system  is  drained  of  blood,  wdiat 
is  to  prevent  the  carbonic  acid  from  accumulating  in  the 
tissues,  and  may  not  this  be  the  cause  of  the  sense  of  want 
of  air! 

I  have  tried  to  imagine  experiments  to  meet  this  ob- 
jection. I  have  tried  to  devise  some  means  of  getting  rid 
of  the  carbonic  acid  from  the  tissues,  that  will  not  at  the 
same  time  either  supply  oxygen  or  send  through  the  tis- 
sues a  fluid  like  blood,  containing  carbonic  acid.  This 
flaw  in  my  argument  I  can  not  correct  experimentally. 

One  other  important  point  in  this  connection,  which 
may  be  of  more  interest  to  some  of  my  hearers  than  those 
to  which  I  have  thus  far  called  attention,  is  the  cause  of  the 
first  respiratory  effort  made  by  the  newborn  child. 

Many  of  the  ancient  writers  regarded  the  placenta  as 
the  respiratory  organ  of  the  foetus;  and  it  is  now  known 
positively  that  the  foetus  in  utero  gets  its  oxygen  from  the 
blood  of  the  mother  through  the  placental  vessels;  but 
when  the  child  is  born,  this  source  of  supply  of  oxygen  is 
cut  off  and  the  first  act  of  pulmonary  respiration  is  per- 
formed, this  being  the  beginning  of  the  function  which 
continues  to  the  end  of  life. 


122  NERVOUS    ACTION    IN    RESPIRATION 

What  is  the  exciting  cause  of  this  first  respiration!  It 
has  been  shown  positively,  by  experiments  upon  animals, 
that  the  first  respiration  is  clue  to  an  arrest  of  the  placental 
circulation.  1  have  frequently  opened  the  abdomen  of  dogs 
and  cats  big  with  young  and  taken  the  young  from  the 
uterus,  when  they  had  hardly  attained  one-fourth  of  their 
size  at  term,  have  laid  them  on  a  table,  and  respiratory 
movements  have  always  occurred  in  a  very  short  time  after 
they  were  separated  from  the  mother.  Experiments  have 
been  made  upon  animals,  by  opening  the  abdomen  and 
pressing  upon  the  umbilical  cord;  and  in  a  short  time  re- 
spiratory movements  have  occurred. 

It  is  well  known  to  gynecologists  and  obstetricians 
that  respiratory  movements  occasionally  occur  in  the  hu- 
man foetus  in  utero  as  a  consequence  of  some  interference 
with  the  placental  circulation;  and  the  amniotic  fluid  and 
even  meconium  have  been  found  in  the  respiratory  pas- 
sages. 

A  very  thorough  exposition  of  these  facts  has  lately 
been  made  by  Dr.  B.  S.  Schultze,  in  a  work  published  at 
Jena,  in  1871,  entitled  "  Der  Scheintod  Neugeborener,"  in 
which  the  points  I  have  stated  are  so  fully  set  forth  that 
there  can  be  no  doubt  upon  the  subject.  It  seems  to  me 
that  the  respiratory  efiforts  before  birth  constitute  a  very 
strong  argument  in  favor  of  the  view  that  I  have  stated; 
and  it  seems  to  me  certain  that  the  first  respiratory  move- 
ments after  birth  are  due  to  the  following  conditions:  The 
placental  circulation  is  arrested;  the  new  being  feels  the 
sense  of  the  want  of  air;  and  the  impression  is  conveyed 
to  the  medulla  oblongata,  where  a  stimulus  is  generated 
which  is  carried  by  motor  nerves  to  the  inspiratory  mus- 
cles. The  inspiratory  muscles  then  contract,  and  thus  the 
lungs  are  for  the  first  time  distended  with  air. 

The  general  results  of  the  experiments  that  I  have  de- 
tailed this  evening,  and  which,  I  may  say,  I  have  performed 
over  and  over  again,  are  the  following: 

Respiration  is  a  reflex  phenomenon.  The  movements 
of  respiration  are  reflex.  There  is  a  special  respiratory 
nerve-centre,  which  is  situated  in  the  medulla  oblongata. 
When  this  nerve-centre  is  destroyed,  no  respiratory  move- 
ments can  take  place,  because  there  is  no  centre  to  receive 
the  impression  of  want  of  air.     Respiratory  movements 


NERVOUS    ACTION    IN    RESPIRATION  123 

are  due  to  an  impression  made  upon  the  centripetal  nerves; 
and  this  impression  is  due  to  a  want  of  oxygen  in  the 
general  system.  The  sympathetic  system  may  possibly  be 
involved  in  this  action,  but  this  point  has  not  been  de- 
termined. The  sense  of  the  want  of  air,  conveyed  to  the 
medulla  oblongata,  gives  rise,  under  ordinary  conditions, 
to  respiratory  movements,  which  take  place  without  the 
consciousness  of  the  individual.  Under  ordinary  condi- 
tions respiration  is  carried  on  by  the  medulla  oblongata 
and  does  not  involve  the  action  of  the  brain.  \\'henever 
there  is  any  difficulty  in  respiration,  the  sense  of  want  of 
air  is  exaggerated  until  it  becomes  a  sense  of  suffocation, 
which  involves  voluntary  efforts  on  the  part  of  the  indi- 
vidual to  supply  the  want  of  air. 


VII 

EXPERIMENTS  ON  THE  EFFECTS  UPON  RES- 
PIRATION OF  CUTTING  OFF  THE  SUPPLY 
OF  BLOOD  FROM  THE  BRAIN  AND  ME- 
DULLA OBLONGATA 

Published  in  the  "  New  York  Medical  Journal  "  for  November,  1877. 

In  October,  1861,  I  published  in  the  "  American  Jour- 
nal of  the  Medical  Sciences  "  a  paper  on  "  Points  connected 
with  the  Action  of  the  Heart  and  with  Respiration."  In 
this  paper  I  contended  that  the  respiratory  sense,  "  besoin 
de  respirer,"  of  the  French,  or  sense  of  want  of  air,  which 
gives  rise  to  the  movements  of  respiration,  is  due  to  a  want 
of  oxygen  in  the  general  system.  I  assumed  that  in  the 
medulla  oblongata  is  to  be  found  the  centre  presiding 
over  the  respiratory  movements;  that  these  movements  are 
reflex;  that  a  certain  sense,  called  the  respiratory  sense, 
is  conveyed  to  the  medulla  oblongata;  and  that  it  is  this 
sense  which  is  the  starting-point  of  the  respiratory  acts.  I 
showed  that  a  dog  brought  under  the  influence  of  ether, 
with  the  heart  and  lungs  exposed  and  with  a  bellows  in 
the  trachea,  will  make  no  respiratory  elTorts  so  long  as  air 
is  efficiently  supplied  to  the  lungs  by  artificial  respiration, 
an  experiment  essentially  the  same  as  one  made  by  Robert 
Hooke,  in  1664.  In  an  animal  in  this  condition,  I  showed 
that  respiratory  efforts  were  made,  when  artificial  respira- 
tion was  interrupted,  so  soon  as  the  blood  became  dark  in 
the  arteries,  having  opened  an  artery  and  noted  the  color 
of  the  blood  as  the  experiment  progressed. 

It  seemed  to  me  at  that  time  that  the  sense  of  want  of 
air  in  this  experiment  was  due  to  the  properties  of  the  dark- 
colored  blood  circulating  in  the  arterial  system;  and  the 
question  arose  in  my  mind  whether  this  was  dependent 
upon  the  deficiency  of  oxygen  in  the  blood  or  upon  the 
presence  of  carbonic  acid.  In  order  to  answer  this  ques- 
124 


MEDULLA   OBLONGATA    AND   RESPIRATION     125 

tion,  I  drained  an  animal  (a  good-sized  dog)  of  blood  by 
dividing  the  femoral  artery,  the  chest  having  been  opened 
with  the  animal  under  the  influence  of  ether  and  artificial 
respiration  being  maintained  in  the  usual  way.  In  this  ex- 
periment, although  the  lungs  were  fully  supplied  with  air, 
violent  respiratory  efforts  were  made  as  the  animal  became 
nearly  exsanguine. 

In  another  experiment  I  divided  both  pneumogastric 
nerves  and  ascertained  that  there  was  no  difference  in  the 
phenomena  observed,  showing  that  these  nerves  are  not 
the  sole  conductors  of  the  sense  of  want  of  air.  In  still 
another  experiment  I  drained  an  animal  of  blood  by  cut- 
ting out  the  heart.  This  was  followed  by  violent  respira- 
tory efforts,  showing  that  the  sense  of  want  of  air  has  noth- 
ing to  do  with  distension  of  the  right  cardiac  cavities. 

From  the  experiments  of  which  I  have  thus  given  a 
brief  sketch,  made  in  1861,  I  concluded  that  the  sense  of 
want  of  air,  or  the  respiratory  sense,  was  due  to  a  want 
of  oxygen  in  the  general  system,  producing  an  impression 
which  was  conveyed  to  the  medulla  oblongata  and  which 
gave  rise  to  respiratory  efforts;  that  in  ordinary  respiration, 
this  reflex  action  took  place  unconsciously,  but  became 
exaggerated  when  there  was  a  great  deficiency  of  oxygen 
and  was  then  experienced  as  a  sense  of  suffocation ;  that  the 
respiratory  sense  thus  had  its  origin  in  the  general  system 
and  not  in  the  lungs,  as  the  sense  of  thirst  has  its  seat  in 
the  general  system,  from  deficiency  of  water,  and  has  sim- 
ply a  local  manifestation  in  dryness  of  the  throat  and  fau- 
ces. In  addition  to  the  experimental  arguments  in  favor 
of  this  view,  I  saw,  in  cases  of  distress  in  breathing  from 
deficient  circulation,  as  in  certain  cases  of  disease  of  the 
heart  in  which  the  lungs  are  normal,  what  seemed  to  me 
to  be  a  confirmation  of  my  opinion. 

The  views  which  I  have  just  stated  were  advanced  by 
me  in  my  work,  "  Physiology  of  Man."  New  York,  1866, 
vol.  i.,  page  479,  et  scq.,  and  in  my  "  Text-Book  of  Human 
Physiology,"  New  York,  1876,  page  164,  et  scq.  In  Feb- 
ruary, 1874,  I  made  an  address  before  the  New  York  So- 
ciety of  Neurology  and  Electrology  upon  the  "  Mechanism 
of  Reflex  Nervous  Action  in  Normal  Respiration,"  an  ab- 
stract of  which  was  published  in  the  "  New  York  Medical 
Journal,"  in  April  of  the  same  year.     The  full  text  of  this 


126    MEDULLA  OBLONGATA   AND    RESPIRATION 

address  was  published  in  the  "  Chicago  Journal  of  Nervous 
and  Mental  Diseases,"  in  April,  1874.  In  this  I  still  ad- 
hered to  my  original  view,  and  I  extended  my  reflections 
to  the  theory  of  the  cause  of  the  first  respiration  at  birth, 
respiration  in  utero  by  means  of  the  placenta,  etc. 

At  the  present  day  nearly  all  physiological  writers  agree 
that  the  sense  of  want  of  air  is  due  to  want  of  oxygen  and 
not  to  any  stimulating  or  irritating  properties  of  carbonic 
acid;  and  this  idea  has  received  confirmation  from  the  ex- 
periments of  Pfliiger  upon  the  effects  of  respiration  of  ni- 
trogen, as  is  seen  by  the  following  extract: 

"  Using  bloodletting  for  ascertaining  the  condition  of  the  blood 
during  dyspnoea,  I  arrived  at  the  following  facts :  As  soon  as  the 
dog  begins  to  breathe  pure  nitrogen,  it  is  scarcely  fifteen  seconds 
before  he  makes  violent  and  deep  inspirations-;  at  the  end  of  thirty 
seconds,  the  most  intense  dyspnoea  is  observed,  the  blood  is  already 
almost  absolutely  black,  which  must  be  due  to  the  enormously 
rapid  tissue-metamorphosis  of  this  animal."  * 

It  is  seen  that  this  experiment,  made  in  1868,  is  almost 
identical  in  its  idea  and  results  with  those  which  I  made  in 
1 861,  except  that  Pfliiger  made  his  animal  breathe  a  gas 
not  capable  of  supporting  respiration,  while  I  simply  de- 
prived animals  of  air.  Nearly  the  same  experiment  as  that 
performed  by  Pfli.iger  was  made  by  Rosenthal,  in  1862, 
who  noted  that  animals  suffered  no  dyspnoea  when  air  or 
oxygen  was  forced  through  the  lungs,  but  that  dyspnoea 
was  manifested  when  nitrogen  or  hydrogen  was  used  in- 
stead of  oxygen. f 

While  physiologists  are  now  pretty  generally  agreed 
that  the  sense  of  want  of  air  is  connected  with  a  deficiency 
of  oxygen  in  the  blood  of  the  arteries,  some  writers  are  of 
the  opinion  that  the  "  sense  "  is  primarily  due  to  a  want 
of  oxygenated  blood  circulating  in  the  medulla  oblongata. 
This  opinion  has  been  advanced  by  some  authors,  but  so 
far  as  I  know  it  rests  mainly  upon  theory  and  has  no  posi- 
tive experimental  foundation.  Since  I  made  the  experi- 
ments which  form  the  basis  of  this  article,  I  have  consulted 
a  number  of  systematic  works  upon  physiology  with  refer- 

*  Pfliiger,  "  Ueber  die  Ursache  der  Athembewegungen,  sowie  der  Dys- 
pnoe  und  Apnoe." — "Archiv  fur  die  gesammte  Physiologie,"  Bonn,  1868,  Bd^ 
i.,  S.  8q. 

t  Rosenthal,  "  Athembewegungen,"  etc.,  Berlin,  1862,  S.  4. 


MEDULLA  OBLONGATA   AND    RESPIRATION    127 

ence  to  the  subject  under  consideration.  Most  of  the 
works  examined  contain  no  very  definite  allusions  to  the 
respiratory  sense,  or  at  most  only  brief  and  unsatisfactory 
statements;  but  in  two,  I  find  the  following  references  that 
are  directly  pertinent  to  the  question: 

"  The  first  respiratory  effort  of  the  foetus  is  thus  produced  by 
the  interruption  of  the  placental  respiration,  the  sudden  deficiency 
of  oxygen  and  increase  of  carbonic  acid  in  the  blood  (Schwartz). 
This  change  in  the  blood  needs  to  take  place  locally  only  in  the 
vessels  of  the  medulla  oblongata,  in  order  to  produce  this  effect; 
it  occurs,  for  example,  from  arrest  of  the  blood  in  these  vessels 
(by  ligature  of  the  carotid  arteries,  Kussmaul  and  Tenner,  Rosen- 
thal, or  by  closure  of  the  venous  currents  from  the  brain,  Hermann 
and  Escher),  by  w^hich  their  blood  becomes  progressively  poorer 
in  oxygen  and  richer  in  carbonic  acid  "  (Hermann,  "  Grundriss  der 
Physiologie  des  Menschen,"  Berlin,  1870,  S.  160). 

"  If  the  supply  of  blood  be  cut  off  from  the  medulla  by  ligature 
of  the  blood-vessels  of  the  neck,  dyspnoea  is  produced,  though  the 
operation  produces  no  change  in  the  blood  generally,  but  simply 
affects  the  respiratory  condition  of  the  medulla  itself,  by  cutting 
off  its  blood-supply,  the  immediate  result  of  which  is  an  accumu- 
lation of  carbonic  acid  and  a  paucity  of  available  oxygen  in  the 
protoplasm  of  the  nerve-cells  in  that  region"  (Foster,  "A  Text- 
Book  of  Physiology,"  London,  1877,  p.  254). 

These  quotations  from  Hermann  and  from  Foster  show 
clearly  that  their  idea  is  that  the  sense  of  want  of  air  is 
due  to  deficiency  of  oxygenated  blood  in  the  medulla  ob- 
longata, a  view  fully  sustained  by  my  own  experiments. 
The  observations  of  Kussmaul  and  Tenner,  referred  to  by 
Hermann,  were  made  with  reference  to  the  cause  of  the 
convulsions  which  so  often  occur  after  profuse  and  sudden 
hemorrhage.  They  are  to  be  found  in  the  elaborate  mem- 
oir by  Kussmaul  and  Tenner,  "  On  the  Nature  and  Origin 
of  Epileptiform  Convulsions  caused  by  Profuse  Bleeding," 
translated  and  published  by  the  "  New  Sydenham  Soci- 
ety," in  1859.  Kussmaul  and  Tenner  made  a  large  num- 
ber of  experiments  on  rabbits  and  horses,  in  which  they 
observed  the  effects  of  tying  the  great  vessels  given  off 
from  the  arch  of  the  aorta.  They  noted,  after  this  opera- 
tion, great  difficulty  in  respiration  and  violent  convulsions. 
They  did  not,  however,  abolish  the  respiratory  movements 
of  the  animal  by  artificial  respiration,  thus  abolishing,  for 
the  time,  the  respiratory  sense,  and  then  note  the  effects 
of  ligature  of  these  vessels.    The  experiments  by  Rosenthal. 


128    MEDULLA   OBLONGATA    AND    RESPIRATION 

which  are  referred  to,  are  probably  those  contained  in  his 
work  on  "  Die  Athembewegungen  und  ihre  Beziehungen 
zum  NervLis  Vagus,"  Berhn,  1862.  In  these  experiments, 
as  I  have  already  stated,  it  is  shown  that  the  respiratory 
efforts  of  an  animal  can  be  abolished  by  forcing  atmos- 
pheric air  or  oxygen  in  large  quantities  through  the  lungs; 
but  that  the  sense  of  want  of  air  is  felt  when,  in  place  of 
oxygen,  nitrogen  or  hydrogen  is  employed,  by  this  means 
removing  the  possibility  of  an  irritation  from  carbonic  acid. 
These  are  essentially  the  same  as  the  observations  made 
by  Pfliiger,  in  1868.  Rosenthal  states  very  distinctly  that 
the  sense  of  want  of  air  is  due  to  want  of  oxygen-carrying 
blood  in  the  medulla  oblongata;  but  he  does  not  actually 
demonstrate  the  truth  of  this  proposition  by  experiments. 
The  statements  by  Hermann  and  by  Foster  are  apparently 
based  upon  the  experiments  of  Kussmaul  and  Tenner  and 
of  Rosenthal;  but  I  must  nevertheless  claim  that  the  ex- 
periments which  I  have  made  upon  this  subject,  which  will 
be  detailed  farther  on,  if  they  should  be  confirmed,  afford 
the  first  positive  proof  that  the  respiratory  sense  may  be 
excited  by  cutting  off  the  arterial  supply  from  the  medulla. 
There  is  nothing  which  I  can  find  in  the  experiments  of 
Kussmaul  and  Tenner  or  of  Rosenthal  to  actually  show 
that  the  sense  of  want  of  air  is  not  due  to  a  want  of  oxy- 
gen in  the  general  system. 

In  reflecting  upon  this  subject  during  the  last  few 
months,  it  occurred  to  me  that  the  question  was  capable 
of  a  positive  solution  by  experiment.  If  it  is  possible  to 
cut  off  the  arterial  supply  to  the  head  and  medulla  oblon- 
gata, leaving  the  rest  of  the  circulation  free,  an  animal 
should  make  respiratory  efforts,  even  though  air  is  supplied 
to  the  lungs,  provided  that  the  sense  of  want  of  air  is  due 
to  a  want  of  oxygenated  blood  in  the  medulla.  On  the 
other  hand,  if  the  sense  of  want  of  air  is  due  to  a  want  of 
oxygen  in  the  general  system,  cutting  off  the  arterial  sup- 
ply from  the  head  and  medulla  would  have  no  more  effect 
than  cutting  off  the  supply  of  oxygen  from  any  other  equal- 
ly extensive  part  of  the  system.  In  reducing  this  idea  to 
the  project  of  an  actual  experiment,  I  conceived  the  follow- 
ing: I  proposed  to  tie  the  vessels  of  supply  to  the  medulla 
oblongata  (the  vessels  given  off  from  the  arch  of  the  aorta) 
and  note  the  effects;  and  then  to  tie  the  descending  aorta 


MEDULLA   OBLONGATA   AND    RESPIRATION     129 

in  the  chest  and  note  the  effects,  leaving  the  vessels  com- 
ing from  the  arch  of  the  aorta  free.  It  seemed  to  me  that 
if  the  respiratory  sense  is  due  to  want  of  oxygen  in  the 
general  system,  tying  the  aorta  in  the  chest  would  induce 
respiratory  efforts  as  promptly  as  cutting  off  the  arterial 
supply  from  the  medulla.  With  the  view  of  settling  this 
question  if  possible,  I  made  the  following  experiments, 
which  so  far  as  they  go  are  definite  and  satisfactory  in 
their  results.  I  propose,  however,  to  extend  these  experi- 
ments, and  I  publish  them  now  simply  as  preliminary  to 
further  investigations  into  the  subject: 

Experiment  I.,  September  30,  1877. — A  medium-sized,  full- 
grown  dog  was  brought  completely  under  the  influence  of  ether. 
The  trachea  was  then  opened  and  connected  with  a  bellows  and 
artificial  respiration  was  maintained.  Over  the  valve  of  the  bel- 
lows was  placed  a  sponge,  which  was  saturated  with  ether  from 
time  to  time,  so  that  the  animal  was  kept  completely  anesthetized 
during  the  experiment.  The  air  in  the  bellows  was  also  changed 
from  time  to  time  by  pushing  up  the  valve  with  the  fingers  and  for- 
cing out  the  vitiated  air.  The  chest  and  abdomen  were  then  laid 
open  by  a  continuous  incision  in  the  median  line,  and  the  ribs  were 
bent  backward  and  secured  with  a  strong  cord  tied  behind  the 
"back,  so  that  the  lungs  and  heart  were  fully  exposed.  The  peri- 
cardium was  then  cut  away,  the  great  vessels  near  the  heart  were 
isolated  and  loose  ligatures  were  thrown  around  the  trunk  of  the 
innominate  artery,  the  left  subclavian  artery,  the  descending  vena 
cava,  the  descending  portion  of  the  aorta  and  the  ascending  vena 
cava.*  In  this  way,  I  was  prepared  to  constrict  the  several  vessels 
at  will. 

When  these  preliminary  steps  had  been  completed,  the  animal 
being  entirely  vmder  the  influence  of  ether  and  artificial  respira- 
tion being  kept  up  efficiently,  there  were  absolutely  no  respiratory 
efforts,  and  the  diaphragm,  which  was  exposed,  was  quiescent. 

The  artificial  respiration  was  then  arrested.  In  forty-five  sec- 
onds the  animal  began  to  make  violent  respiratory  efforts.  Artifi- 
cial respiration  was  then  resumed  and  the  respiratory  efforts  of 
the  animal  ceased.  When  the  artificial  respiration  was  arrested, 
I  first  noticed  a  movement  of  the  corners  of  the  mouth  at  regular 
intervals  and  then  the  mouth  was  widely  opened  and  the  diaphragm 
became  strongly  contracted,  also  at  regular  intervals.  The  time 
was  taken  at  the  first  violent  respiratory  effort. 

The  animal  being  quiet  and  making  no  efforts  at  respiration, 
the  innominate  artery,  the  left  subclavian  artery  and  the  descend- 

*  In  the  dosf  the  aorta  gives  off  the  innominate  artery  "which  gives  off 
first  the  left  carotid,  and  then  divides  into  the  right  subclavian  and  right  ca- 
rotid "  (Foster,  "  Elementary  Practical  Physiology,"  London,  1876,  p.  13).  The 
left  subclavian  artery  arises  directly  from  the  aorta. 

9 


I30    MEDULLA  OBLONGATA   AND    RESPIRATION 

ing  vena  cava  were  tied  almost  simultaneously,  artificial  respiration 
being  constantly  and  efficiently  maintained.  In  two  minutes  and 
eight  seconds  the  animal  began  to  make  respiratory  efforts,  which 
continued  so  long  as  the  vessels  remained  constricted. 

The  ligatures  surrounding  the  vessels  mentioned  above  were 
loosened  five  minutes  and  twenty-two  seconds  after  they  had  been 
tied,  and  the  respiratory  efforts  of  the  animal  instantly  ceased. 
After  three  minutes,  artificial  respiration  was  stopped,  and  the 
animal  began  to  make  respiratory  efforts  in  thirty-nine  and  a  half 
seconds,  which  ceased  so  soon  as  artificial  respiration  was  re- 
sumed. 

The  descending  aorta  and  the  ascending  vena  cava  in  the  chest 
were  then  tied  simultaneously,  the  vessels  arising  from  the  arch 
of  the  aorta  being  free.  This  seemed  to  produce  no  effect,  and  no 
respiratory  efforts  were  made  by  the  animal  for  five  minutes.  The 
innominate  artery  and  the  left  subclavian  artery  were  then  con- 
stricted, the  aorta  and  ascending  vena  cava  remaining  tied.  Re- 
spiratory efforts  by  the  animal  began  in  one  minute  and  twenty-six 
seconds,  although  artificial  respiration  was  maintained.  These  ef- 
forts ceased  when  the  ligatures  around  the  innominate  and  sub- 
clavian were  loosened. 

The  ligatures  were  then  removed  from  the  descending  aorta 
and  ascending  vena  cava,  and  the  innominate  and  left  subclavian 
arteries  were  constricted,  which  was  followed  by  respiratory  efforts 
after  one  minute  and  six  seconds.  These  efforts  ceased  when  the 
vessels  were  freed. 

The  innominate  artery  alone  was  then  constricted,  but  this 
seemed  to  produce  no  effect,  no  respiratory  efforts  being  made  by 
the  animal  for  five  minutes.  At  the  end  of  five  minutes  the  left 
subclavian  artery  was  constricted,  the  constriction  of  the  innomi- 
nate artery  being  maintained.  The  animal  began  to  make  respira- 
tory efforts  fifty-three  seconds  after  constriction  of  the  subclavian. 
These  eff'orts  ceased  on  loosening  the  ligatures. 

Artificial  respiration  was  then  stopped  and  the  animal  began  to 
make  respiratory  efforts  in  ten  seconds.  The  medulla  oblongata 
was  then  broken  up  and  the  experiment  was  concluded. 

In  this  experiment  I  had  the  aid  of  my  assistant.  Dr.  C.  F. 
Roberts,  and  of  Mr.  Caspar  Griswold,  an  advanced  laboratory 
student.  As  the  experiment  progressed,  it  was  ascertained  that  the 
vessels  could  be  effectually  constricted  by  making  traction  on  the 
ligatures  without  tying.  The  constriction  could  then  be  instantly 
removed.  It  was  also  ascertained  that  constriction  of  the  veins 
made  no  difference  in  the  phenomena  observed. 

Experiment  II.,  October  2,  1877. — A  medium-sized,  full-grown 
dog  was  brought  completely  under  the  influence  of  ether.  A  bel- 
lows was  fixed  in  the  trachea  and  the  chest  and  abdomen  were 
opened  as  in  the  preceding  experiment.  These  preliminary  steps 
were  completed  at  11.30  a.  m.  Artificial  respiration,  which  had 
been  kept  up  with  the  bellows,  was  arrested  and  the  animal  made 
efforts  at  respiration  in  thirty-seven  and  three-fifth  seconds,  having 
previously  been  quiet.     The  innominate  artery  and  the  left  subcla- 


MEDULLA  OBLONGATA   AND    RESPIRATION     131 

vian  artery  were  then  constricted,  the  artificial  respiration  being 
continued,  and  the  animal  made  respiratory  efforts  in  two  minutes 
and  five  seconds,  having  previously  been  rendered  quiet  by  artificial 
respiration.  After  a  few  respiratory  efforts  the  ligatures  were 
loosened  and  the  animal  became  perfectly  quiet,  artificial  respira- 
tion being  continued.  While  the  animal  was  perfectly  quiet,  artifi- 
cial respiration  being  continued,  the  descending  aorta  was  tied  in 
the  chest.  The  aorta  was  constricted  for  five  minutes  and  no  effect 
was  observed,  artificial  respiration  being  maintained  and  the  animal 
remaining  perfectly  quiet.  The  heart  was  then  cut  out,  the  system 
being  thus  drained  of  blood,  and  the  animal  made  respiratory  efforts 
in  twenty-five  seconds. 

This  experiment  was  a  public  demonstration  made  in  a  lecture 
before  the  class  at  the  Bellevue  Hospital  Medical  College ;  and  I 
was  assisted  by  Dr.  C.  F.  Roberts,  Mr.  Caspar  Criswold,  Dr.  C.  S. 
Conant  and  Mr.  W.  L.  Wardwell.  The  experiment  was  essentially 
a  repetition  of  Experiment  I.,  and  the  results  of  the  two  observa- 
tions were  nearly  identical. 

The  two  experiments  just  detailed  show  that  ligature 
of  the  aorta  has  no  sensible  effect  upon  respiration;  but 
that  ligature  of  all  the  vessels  given  off  from  the  arch  of 
the  aorta,  w-hich  it  would  seem  must  cut  off  most  of  the 
supply  of  oxygenated  blood  from  the  brain  and  the  medulla 
oblongata,  produces  a  sense  of  want  of  air,  which  gives 
rise  to  respiratory  efforts,  even  while  artificial  respiration 
is  efficiently  maintained.  It  seems,  from  the  results  ob- 
served in  Experiment  I.,  that  it  is  not  enough  to  tie  the 
innominate  artery,  which  is  equivalent  to  tying  the  two 
common  carotids  and  the  right  subclavian  artery,  but  that 
it  is  necessary  to  tie  also  the  left  subclavian  artery.  This 
is  explained  by  the  fact  that  the  left  subclavian  gives  off 
the  vertebral  artery,  which  empties  into  the  basilar  artery 
and  thus  carries  oxygenated  blood  to  the  medulla  oblon- 
gata. 

Taking  into  account  the  fact  that  the  respiratory  nerve- 
centre  is  situated  in  the  medulla  oblongata,  the  two  experi- 
ments that  I  have  described,  so  far  as  they  go,  seem  to 
show  conclusively  that  the  sense  of  want  of  air  is  due  to 
a  deficiency  of  oxygenated  blood  in  the  medulla  oblongata, 
and  that  this  sense  is  satisfied  bv  the  circulation  of  such 
blood  in  the  respiratory  nerve-centre. 

Experiment  III.,  October  7,  1877. — A  full-grown  young  dog, 
weighing  about  thirty  pounds,  was  brought  completely  under  the 
influence  of  ether  at  10.45  a.  m.,  a  bellows  was  fixed  in  the  trachea, 
and  the  chest  and  abdomen  were  opened  as  in  the  preceding  ex- 


132    MEDULLA    OBLONGATA   AND    RESPIRATION 

periments.  The  vessels  given  off  from  the  arch  of  the  aorta  w^ere 
then  carefully  dissected  out,  and  loose  ligatures  were  thrown 
around  the  innominate  artery,  the  two  carotids,  the  right  subclavian 
artery,  the  right  vertebral  artery,  the  left  subclavian  artery  and  the 
left  vertebral  artery.  These  ligatures  were  placed  around  the  ves- 
sels so  that  they  might  be  readily  found  in  the  course  of  the  experi- 
ment, but  the  vessels  were  not  thereby  constricted. 

After  these  preparatory  steps  had  been  completed,  artificial 
respiration  was  arrested  and  the  animal  began  to  make  respiratory 
efforts  in  thirty  seconds.  Artificial  respiration  was  then  resumed 
and  the  animal  became  quiet. 

The  two  subclavian  arteries  were  then  constricted  with  scrre- 
iincs,  which,  it  was  ascertained,  arrested  the  blood-current  com- 
pletely. The  animal  remained  quiet  for  five  minutes,  making  no 
respiratory  efforts.  The  subclavians  remaining  constricted,  both 
carotids  were  then  constricted  in  addition.  The  animal  made  re- 
spiratory efforts  in  two  minutes  and  seven  seconds  after  constric- 
tion of  the  carotids.  All  the  vessels  were  then  freed  and  the  ani- 
mal became  quiet. 

Both  vertebral  arteries  and  both  carotids  were  then  constricted 
for  five  minutes,  the  animal  remaining  quiet.  These  vessels  re- 
maining constricted,  both  subclavian  arteries  were  constricted  in 
addition.  The  animal  made  respiratory  efforts  in  one  minute  and 
thirty-five  seconds.  All  the  vessels  were  then  freed,  and  the  ani- 
mal became  quiet. 

At  11.40  o'clock  the  descending  aorta  in  the  chest  and  both 
subclavian  arteries  were  tied.  This  left  little  more  than  the  carot- 
ids to  carry  blood  to  the  head,  and  the  arterial  blood  was  thus 
cut  off  from  the  greatest  part  of  the  system.  The  animal  remained 
quiet  for  five  minutes.  The  experiment  had  now  lasted  fifty-five 
minutes  and  the  action  of  the  heart  had  become  considerably  weak- 
ened. While  the  aorta  and  subclavians  were  still  constricted,  both 
carotids  were  constricted  in  addition.  The  animal  remained  quiet 
for  five  minutes,  but  the  heart  and  the  great  vessels  up  to  the 
points  of  constriction  were  enormously  distended.  At  the  end  of 
this  time  the  aorta  was  freed,  which  relieved  the  distension.  The 
animal  made  respiratory  efforts  in  two  minutes  and  twenty-nine 
seconds,  but  the  efforts  were  not  very  violent  and  were  not  so 
rapid  as  usual.  All  the  vessels  were  freed  and  the  animal  became 
quiet. 

Artificial  respiration  was  then  arrested  and  the  animal  made 
respiratory  efforts  in  twelve  seconds.  Artificial  respiration  was 
resumed  and  the  animal  became  quiet. 

The  innominate  artery  and  the  left  subclavian  artery  were  then 
constricted  and  the  animal  made  respiratory  efforts  in  one  minute 
and  fifteen  seconds,  but  the  action  of  the  heart  had  become  very 
feeble. 

The  experiment  had  lasted  one  hour  and  fifteen  minutes  and 
was  concluded  with  the  last  observation. 

In  this  experiment  I  was  assisted  by  Dr.  C.  F.  Roberts,  Mr. 
Caspar  Griswold  and  Dr.  G.  S.  Conant. 


MEDULLA   OBLONGATA   AND    RESPIRATION    133 

This  experiment  substantially  confirmed  the  results  ob- 
tained in  Experiments  L  and  IL  When  the  aorta,  both 
subclavian  arteries  and  both  carotids  were  constricted,  the 
pressure  of  blood  in  these  vessels  was  enormous,  and  some 
blood  may  have  found  its  w-ay  to  the  brain  and  medulla 
oblongata.  The  distension  of  the  vessels  was  so  great  that 
this  part  of  the  experiment  was  not  very  satisfactory.  Re- 
spiratory efforts  were  made  by  the  animal,  however,  when 
the  distension  was  relieved  by  freeing  the  aorta,  the  subcla- 
vians  and  the  carotids  remaining  constricted. 

In  all  the  experiments  the  animals  were  kept  complete- 
ly under  the  influence  of  ether,  and  artificial  respiration 
was  kept  up  efficiently  unless  otherwise  stated. 

Deductions  and  Conclusions. — When  I  made  my 
first  experiments  on  the  seat  of  the  sense  of  want  of  air 
which  gives  rise  to  respiratory  movements,  in  1861,  I 
attached  to  them  considerable  importance;  and  I  thought 
that  I  had  proved  experimentally  that  the  sense  of  want 
of  air  is  due  to  a  deficiency  in  oxygen  in  the  system  at 
large.  The  main  features  of  the  experiments  which  I  made 
at  that  time  I  have  already  stated.  My  object  in  making 
these  new  experiments  was  to  study  the  effects  of  cut- 
ting off  the  supply  of  oxygenated  blood  from  different 
parts. 

I  think  it  may  be  assumed,  as  I  have  already  stated, 
that  the  sole  respiratory  nerve-centre  is  in  the  medulla 
oblongata;  and  I  endeavored  to  devise  some  means  of  cut- 
ting off  the  arterial  supply  of  blood  from  this  part.  Ani- 
mals respire  when  all  of  the  encephalic  centres  have  been 
destroyed  except  the  medulla  oblongata,  so  that  it  is  im- 
probable that  cutting  off  the  supply  of  blood  from  the  brain 
would  affect  the  muscles  of  respiration,  provided  artificial 
respiration  is  ei^ciently  maintained.  Blood  can  get  to  the 
medulla  oblongata  from  the  internal  carotids,  which  are 
connected  with  the  circle  of  Willis,  from  the  vertebral  ar- 
teries, which  unite  to  form  the  basilar  artery,*  and  perhaps 
from  other  vessels;  but  it  is  certain  that  if  all  the  arteries 
given  off  from  the  arch  of  the  aorta  are  tied  the  medulla 
must  be  deprived  of  oxygenated  blood. 

In  Experiment  I.  the  innominate  artery  and  the  left 

*  The  basilar  artery  is  much  longer  in  the  dog  than  in  the  human  subject. 


134    MEDULLA   OBLONGATA   AND    RESPIRATION 

sul)clavian  artery  were  constricted  *  and  the  animal  made 
respiratory  efforts  in  two  minutes  and  eight  seconds,  not- 
withstanding that  artificial  respiration  was  kept  up. 

In  Experiment  II.  the  same  vessels  were  constricted 
and  the  animal  made  respiratory  efforts  in  two  minutes 
and  five  seconds. 

In  Experiment  III.  both  suljclavian  arteries  and  both 
carotids  were  constricted  and  the  animal  made  respiratory 
efforts  in  two  minutes  and  seven  seconds.  Both  vertebral 
arteries  and  both  carotids  were  constricted  and  the  animal 
made  no  respiratory  efforts  for  five  minutes;  but  respira- 
tory efforts  were  made  in  one  minute  and  thirty-five 
seconds  after  both  subclavians  had  been  constricted  in 
addition  to  the  vertebrals  and  carotids. 

It  seems  from  all  of  these  experiments  that  in  order 
to  induce  respiratory  efforts  in  an  animal  under  the  in- 
fluence of  ether  and  with  the  lungs  supplied  with  air  by 
artificial  respiration,  either  the  innominate  artery  and  the 
left  subclavian  artery  or  both  subclavians,  both  carotids 
and  both  vertebral  arteries  must  be  tied.  In  other  words, 
according  to  my  view  of  the  cause  of  these  respiratory 
efforts,  the  supply  of  blood  to  the  medulla  oblongata  can 
not  be  cut  off  completely  except  by  tying  all  the  vessels 
given  off  from  the  arch  of  the  aorta. 

As  the  result  of  the  experiments  which  I  have  just 
detailed,  I  must  now  modify  the  view  which  I  advanced 
in  1861  as  a  conclusion  from  experiments  then  published, 
which  I  have  maintained  up  to  the  present  time,  that  the 
sense  of  want  of  air,  which  is  the  starting-point  of  the  move- 
ments of  respiration,  is  due  to  want  of  oxygen  in  the 
general  system.  My  experiments  made  in  1861  were  accu- 
rate and  the  conclusions  from  them  seemed  to  be  legiti- 
mate; but  these  experiments  were  incomplete.  The  ex- 
periments which  I  have  just  reported,  taken  in  connection 
Avith  my  experiments  of  1861,  lead  me  to  conclude  that  the 
sense  of  want  of  air  is  due  to  a  want  of  circulation  of  oxy- 
genated blood  in  the  medulla  oblongata. 

I  trust  that  my  experiments,  which  are  by  no  means 
difficult  or  uncertain  in  their  results,  may  be  repeated  and 

*  In  the  first  experiment  the  great  veins  were  also  tied,  but  this  seemed  to 
make  no  difference  in  the  phenomena  following  con^^triction  of  the  arteries,  and 
the  veins  were  left  free  in  the  other  experiments. 


MEDULLA   OBLONGATA   AND    RESPIRATION    135 

either  verified  or  corrected  by  other  physiologists.  The 
idea  that  the  sense  of  want  of  air  is  due  to  a  deficiency  of 
oxygen  in  the  medulla  has  been  adopted  by  some  writers; 
but  so  far  as  I  know,  my  experiments  are  the  first  to  show, 
by  actual  demonstration,  that  this  view  is  correct. 

In  another  paper  I  propose  to  treat  of  the  respiratory 
sense  much  more  fully  and  to  review  the  literature  of  the 
subject.  Many  interesting  and  important  points  will  un- 
doubtedly be  involved  in  a  full  discussion  of  the  nervous 
mechanism  of  the  respiratory  movements;  and  among  them 
will  be  the  question  as  to  whether  the  normal  respiratory 
movements  are  actually  reflex  in  their  character,  as  has 
been  generally  supposed,  or  whether  they  are  due  to  a 
■direct  excitation  of  the  nerve-cells  in  the  respiratory  centre. 


VIII 

IS  THE  ACTION  OF  THE  MEDULLA  OBLONGA- 
TA IN  NORMAL  RESPIRATION  REFLEX? 

Published  in  the  "  American  Journal  of  the  Medical  Sciences"  for  July,  1880. 

In  connection  with  a  series  of  experiments  published 
in  1877,  the  question  occurred  to  me  whether  or  not  the 
action  of  the  medulla  oblongata  in  normal  respiration  could 
strictly  be  classed  among  those  operations  recognized  by 
physiologists  as  reflex.  That  the  medulla  oblongata  con- 
tains the  centre  presiding  over  certain  reflex  phenomena^ 
acting  through  some  special  nerves,  there  can  be  no  doubt. 
The  centres  in  the  medulla  seem  to  serve  as  coordinators 
of  the  muscles  of  expression,  and  have  certain  reflex  func- 
tions connected  with  the  respiratory  muscles,  such  as 
coughing,  sneezing,  etc.  In  certain  instances,  also,  in 
which  respiration  is  temporarily  suspended,  a  stimulation 
of  parts  of  the  general  surface,  as  by  a  dash  of  cold  water, 
will  excite  respiratory  movements.  Such  an  action  as  the 
one  last  mentioned  might  properly  be  called  reflex;  but 
the  phenomena  which  I  here  propose  to  consider  are  those 
of  ordinary,  normal  respiration  and  the  exaggerations  of 
the  respiratory  sense  which  amount  to  a  more  or  less  in- 
tense feeling  of  want  of  air. 

The  general  view  under  which  physiologists  have  been 
accustomed  to  regard  the  respiratory  movements  as  reflex 
is  the  following:  It  has  been  thought  that  there  existed  in 
some  part  of  the  organism  or  in  the  system  at  large  a 
certain  sense,  which  may  be  called  the  sense  of  want  of 
air,  the  respiratory  sense,  or  the  "  besoin  de  respirer,"  of 
the  French,  dependent  upon  either  an  actual  or  an  im- 
pending deficiency  of  oxygen  or  upon  an  impression  pro- 
duced by  the  circulation  of  blood  containing  carbonic  acid 
in  parts  that  should  normally  receive  oxygenated  blood. 
This  "  respiratory  sense  "  has  been  taken  as  the  starting- 
136 


MEDULLA    IN    NORMAL   RESPIRATION  137 

point  of  the  respiratory  acts.  Regarding  a  reflex  phe- 
nomenon as  involving  an  impression  conveyed  by  afferent 
nerves  to  a  nerve-centre,  which  impression,  by  the  action 
of  the  nerve-centre,  is  converted  into  a  stimulus  and  is 
reflected  along  certain  efterent  nerves  to  muscles,  the  con- 
ditions of  the  operation  of  reflex  action  in  ordinary  respi- 
ration have  been  regarded  as  complete.  The  respiratory 
sense,  according  to  this  view,  is  conveyed  by  certain  cen- 
tripetal nerves  to  the  medulla  oblongata,  and  here  it  is  con- 
verted into  a  stimulus  which  is  conveyed  by  the  proper 
centrifugal  nerves  to  the  respiratory  muscles,  and  there 
follows  an  act  of  inspiration. 

My  principal  object,  in  this  article,  is  to  discuss  the 
question  of  the  so-called  reflex  action  of  the  medulla  ob- 
longata in  respiration,  drawing  conclusions  mainly  from 
my  own  experiments.  I  shall  not,  therefore,  attempt  to 
give  a  full  account  of  the  literature  bearing  upon  the  action 
of  the  medulla  oblongata  as  the  respiratory  nerve-centre 
or  even  of  the  experiments  which  relate  to  its  reflex  func- 
tion, except  in  so  far  as  the  latter  have  been  followed  by 
important  advances  or  changes  in  the  views  of  physiolo- 
gists or  as  their  history  involves  questions  of  priority. 

In  1809  Legallois  made  a  number  of  experiments  upon 
rabbits  in  which  he  showed  that  respiration  ceased  sudden- 
ly when  a  section  of  the  medulla  oblongata  was  made  to 
include  the  origin  of  the  eighth  pair  of  nerves;  but  that 
the  respiratory  acts  continued  when  the  cerebrum,  cere- 
bellum and  a  part  of  the  medulla  oblongata  were  removed 
by  successive  slices  from  before  backward.*  Flourens  ex- 
tended the  observations  of  Legallois  and  fixed  the  limits 
of  the  respiratory  nerve-centre  in  the  rabbit,  between  the 
upper  border  of  the  origin  of  the  pneumogastrics  and  a 
line  drawn  about  a  quarter  of  an  inch  below  the  lowest 
point  of  origin  of  these  nerves. f  Longet  and  Flourens, 
in  later  observations,  restricted  the  limit  still  further,  and 
showed  that  it  was  confined  to  the  gray  matter  of  the  lat- 
eral tracts,  or  the  intermediary  fasciculi.:}:    Since  the  publi- 

*  Legallois,  "  Experiences  sur  le  principe  de  la  vie."  Qiuvres,  Paris,  1824, 
tome  i.,  p.  64.  The  date  of  these  experiments  is  given  by  Legallois  on  page 
71  of  the  above-mentioned  work. 

f  Flourens,  "  Systeme  nerveux,"  Paris,  1842,  p.  204. 

X  Longet,  "  Traite  de  physiologic,"  Paris,  1869,  tome  iii.,  pp.  387,  388. 


138         MEDULLA   IN    NORMAL   RESPIRATION 

cation  of  the  experiments  of  Flourens,  nearly  all  physiolo- 
gists have  agreed  that  the  respiratory  nerve-centre  is  situ- 
ated in  some  part  of  the  gray  matter  of  the  medulla,  and 
this  view  I  accept  without  reserve.  Its  most  notable  op- 
ponent, however,  is  Dr.  Brown-Sequard.  This  author  con- 
tends that  the  arrest  of  respiratory  movements  which  fol- 
lows destruction  of  the  medulla  is  due  to  irritation  of 
surrounding  parts  and  not  to  the  destruction  of  the  so- 
•  called  respiratory  centre;  and  that  in  certain  cases,  the 
movements  may  become  reestal)lishe(l  after  the  irritation 
has  subsided.*  In  the  absence  of  their  full  confirmation 
by  other  observers,  I  do  not  regard  the  experiments  or  the 
conclusions  of  Dr.  Brown-Sequard  as  satisfactory;  and  I 
still  hold  that  the  medulla  oblongata  is  the  centre  presiding 
over  the  respiratory  acts. 

Marshall  Hall,  in  his  memoir  on  the  "  Reflex  Function 
of  the  Medulla  Oblongata  and  Medulla  Spinalis,"  published 
in  1833,  says  nothing  in  regard  to  the  reflex  character  of 
respiration.  In  the  Croonian  Lectures,  delivered  before 
the  Royal  College  of  Physicians  in  1850,  he  advances  the 
view  that  the  normal  respiratory  acts  are  reflex  and  de- 
pendent upon  excitation  of  the  pneumogastric  nerves  by 
the  accumulation  of  carbonic  acid  evolved  in  the  lungs 
from  the  venous  blood. f  Subsequent  observations,  how- 
ever, have  shown  that  the  theory  proposed  by  Marshall 
Hall  is  incorrect;  and  at  the  present  day  it  is  not  adopted  by 
any  ph^ysiologist  of  recognized  authority.  As  early  as  1839, 
John  Reid  suggested  that  the  sense  of  want  of  air  was  due 
in  a  measure  to  the  circulation  of  venous  blood  in  the 
medulla  oblongata.:]:  This  fact  is  interesting  in  view  of  the 
results  of  recent  experiments  which  will  be  detailed  farther 
on.  In  1 84 1  Volkmann  made  a  number  of  experiments, 
the  conclusion  drawn  from  which  was  that  the  sense  of 
want  of  air  depends  upon  a  certain  condition  of  the  general 

*  Brown-S^quard,  "  Recherches  sur  les  causes  de  mort  apres  I'ablation  de  la 
partie  de  la  moelle  allongee  qui  a  ete  nominee  point  vital."  Journal  de  la 
physiologic,  Paris,  1858,  tome  i.,  p.  217  et  seq.  ;  and  "  Recherches  experimen- 
tale  sur  la  physiologie  de  la  moelle  allongee.     Ibid.,  i860,  tome  iii.,  p.  151  et  seq. 

f  Marshall  Hall,  "  Synopsis  of  the  Diastaltic  Nervous  System,"  London  (no 
■date),  p.  43. 

\  Reid,  "An  Experimental  Investigation  into  the  Functions  of  the  Eighth 
Pair  of  Nerves,"  etc..  Part  Second.  "  Anatomical  and  Physiological  Re- 
searches," Edinburgh,  1848,  p.  285;  and  "Edinburgh  Medical  and  Surgical 
Journal,"  April,  1839. 


MEDULLA    IN    NORMAL    RESPIRATION  139 

system  as  well  as  an  impression  made  upon  the  pulmonary 
mucous  membrane. 

"  The  respiratory  movements  appear  really  to  be  of  a  reflex 
character  in  the  following  way :  The  exciting  agent  is  carbonic 
acid — not  that  which  has  become  free  in  the  air  passages,  but  that 
which  is  contained  in  the  blood ;  the  situation  of  the  stimulation 
is  in  every  part  of  the  body,  not  alone  the  pulmonary  mucous  mem- 
brane ;  finally,  the  nerves  brought  into  action  are  all  nerves  which 
conduct  centripetally  operating  toward  the  medulla  oblongata,  not 
exclusively  the  vagus.''  * 

Volkmann  states,  immediately  following  the  passage 
just  quoted,  that  the  respiratory  movements  find  their  im- 
pulse in  a  "  respiratory  necessity  ";  and  that  this  originates 
in  the  eiitire  system;  that  all  animals  require  oxygen  from 
the  blood  in  place  of  the  carbonic  acid  which  they  give 
up  to  the  blood;  and  that  so  soon  as  the  blood  is  over- 
charged with  carbonic  acid,  this  "  necessity  "  (respiratory) 
can  not  be  satisfied. 

In  1 861  I  made  a  series  of  experiments  with  the  view 
of  ascertaining  the  situation  of  the  respiratory  sense,  adopt- 
ing the  view,  which  was  then  almost  universally  received, 
that  the  respiratory  acts  are  reflex. f  The  main  points  in 
these  experiments  were  the  following: 

When  the  chest  was  opened  in  a  living  dog  and  a  bel- 
lows fixed  in  the  trachea,  so  long  as  artificial  respiration 
was  efficiently  performed  the  animal  made  no  respiratory 
efforts.  In  these  experiments  the  animals  usually  were 
etherized;  but  in  several  instances  they  were  allowed  to 
come  from  under  the  influence  of  the  anesthetic.  The  dia- 
phragm and  other  important  respiratory  muscles  were  de- 
nuded and  fully  exposed  to  view.  This  was  almost  an 
exact  repetition  of  an  experiment  performed  by  Robert 
Hooke  in  1664. 

An  artery  was  then  opened  and  the  blood  was  allowed 
to  flow  in  a  small  stream.  When  the  artificial  respiration 
was  suspended  the  animal  began  to  make  respiratory  ef- 
forts so  soon  as  the  blood  became  dark  in  the  arteries;  but 

*  Volkmann,  "  Ueber  die  Bewegungen  des  Athems  und  Schluckens,"  etc. 
"  Archiv  fiir  Anatomie,  Physiologie,  und  wissenschaftliche  Medicin,"  Berlin, 
1841,  S.  342. 

t  Flint,  "  Experimental  Researches  on  Points  connected  with  the  Action 
of  the  Heart  and  vnth  Respiration." — "  American  Journal  of  the  Medical  Sci- 
ences," October,  1861,  p.  372  et  seq. 


I40  MEDULLA   IN    NORMAL    RESPIRATION 

when  artificial  respiration  was  resumed,  so  soon  as  the 
blood  became  again  bright  red  in  the  arteries  the  respira- 
tory efforts  ceased. 

In  order  to  ascertain  whether  the  sense  of  want  of  air 
was  (hie  to  a  deficiency  of  oxygen  or  to  the  presence  of 
carbonic  acid  in  the  blood  of  the  arteries,  I  drained  the 
animals  of  blood,  sometimes  from  a  large  artery  and  some- 
times by  excising  the  heart,  at  the  same  time  keeping  up 
artificial  respiration  carefully  and  efficiently.  As  the  sys- 
tem became  drained  of  blood,  there  always  occurred  vigor- 
ous and  even  violent  respiratory  efforts,  although  the  lungs 
were  kept  supplied  with  pure  air. 

From  these  experiments  I  reasoned  that  the  respira- 
tory movements  being,  as  I  thought,  reflex,  the  sense  of 
want  of  air  depended  upon  a  deficiency  of  oxygen  in  the 
system  at  large  and  not  upon  the  presence  of  carbonic 
acid  in  the  blood  of  the  arteries;  for  the  sense  seemed  to 
be  felt  by  the  animals  in  my  experiments,  when  the  system 
was  drained  of  blood,  the  arteries  containing  no  blood 
charged  with  carbonic  acid. 

In  1868,  about  seven  years  after  the  publication  of  my 
experiments  in  the  "  American  Journal  of  the  Medical  Sci- 
ences," Pfliiger  published  a  very  interesting  article  upon 
the  same  question.*  In  this  article  a  very  elaborate  review 
is  given  of  the  literature  of  the  subject.  He  first  refers  to 
the  opinions  of  various  authors  in  regard  to  the  question 
of  a  difference  in  color  between  the  blood  of  the  um- 
bilical arteries  and  the  umbilical  vein,  and  then  goes  on  to 
state  that  "  it  is  established  without  doubt  that,  after  birth, 
there  is  a  diminution  in  the  quantity  of  oxygen  in  the  body 
of  the  newly  born,  which,  as  the  following  researches  will 
show,  is  the  real  cause  of  respiration."  The  experiments 
which  led  Pfliiger  to  the  conclusion  that  the  sense  of  want 
of  air,  dyspnoea,  and  apnoea  were  due  to  a  want  of  oxygen 
in  the  system  consisted  mainly  in  causing  animals  to 
breathe  an  irrespirable  gas,  such  as  pure  nitrogen. f 

*  Pfliiger,  "  Ueber  die  Ursache  der  Athembewegune:en,  sowie  der  Dvspnoe 
und  Apnoe." — "  Archiv  fur  die  gesammte  Physiologic,"  Bonn,  1S68,  Bd.  i.,  S. 
bl  et  seq. 

\  Rosenthal,  in  his  work  on  the  "Respiratory  Movements,"  published  in 
1862,  anticipated  the  experiments  of  Pfliiger  upon  the  influence  of  the  insuffla- 
tion of  irrespirable  gases  upon  the  respiratory  movements.  He  noted  that  the 
manifestations  of  dyspnoea  ceased  in  animals  when  the  chest  had  been  opened 


MEDULLA    IN    NORMAL    RESPIRATION  141 

"  Using  blood-letting  for  ascertaining  the  condition  of  the  blood 
during  dyspnoea,  I  arrived  at  the  following  facts :  As  soon  as  the 
dog  begins  to  breathe  pure  nitrogen,  it  is  scarcely  fifteen  seconds 
before  he  makes  violent  and  deep  inspirations ;  at  the  end  of  thirty 
seconds,  the  most  intense  dyspnoea  is  observed,  the  blood  is  already 
almost  absolutely  black,  which  must  be  due  to  the  enormously 
rapid  tissue-metamorphosis  of  the  animal.  At  the  end  of  one  min- 
ute the  animal  is  already  almost  asphyxiated.  The  respiratory 
movements  are  very  infrequent  or  have  ceased,  but  the  heart  still 
beats."  * 

Then  follows  a  series  of  examinations  of  the  blood  un- 
der normal  conditions  at  various  times  after  causing  an 
animal  to  breathe  pure  nitrogen.  In  one  of  these  observa- 
tions, after  causing  a  dog  to  breathe  nitrogen  for  one  min- 
ute, the  oxygen  of  the  blood  was  found  to  be  reduced  from 
14.35  P^^  cent,  to  0.2  per  cent.,  and  the  carbonic  acid  from 
36.9  per  cent,  to  29.9  per  cent.,  showing  a  very  great 
diminution  in  oxygen  and  a  considerable  diminution  in  car- 
bonic acid.  "  No  one,  therefore,  can  be  of  the  opinion 
that  dyspnoea  and  asphyxia  in  breathing  indifferent  gases 
is  connected  with  the  accumulation  of  carbonic  acid."  f 

While  Pfliiger  assumed  to  give  a  review  of  the  literature 
of  the  subject  under  investigation,  he  made  no  mention 
of  my  experiments  published  in  1861,  although  the  results 
were  nearly  identical  with  his  own.  Later  observations 
and  experiments,  however,  have  convinced  me  that  the 
interpretations  of  my  earlier  experiments,  as  well  as  those 
made  by  Pfliiger,  were  incorrect.  I  do  not  now  believe 
that  the  acts  of  respiration  are  purely  reflex  in  the  sense 
in  which  this  term  is  generally  used;  and  I  do  not  believe 
that  the  sense  of  want  of  air  is  due  to  a  deficiency  of  oxy- 
gen in  the  system  at  large.  I  have  become  convinced,  by 
experiments  made  in  1877,  that  the  real  cause  of  the  sense 
of  want  of  air,  with  its  various  exaggerations  and  modifi- 
cations,  is  a  deficiency  in  or  an  absence  of  oxygenated 

and  oxygen  was  passed  through  the  lungs,  but  that  they  continued  when,  instead 
of  oxygen,  nitrogen  or  hydrogen  was  used,  "  although  in  this  case  the  carbonic 
acid,  as  well  as  the  oxygen,  was  removed  from  the  blood."  From  this  it  appears 
to  follow  that  it  is  not  the  increased  quantity  of  carbonic  acid,  but  the  dimin- 
ished quantity  of  oxygen  which,  in  dyspnoea,  produces  the  mediate  or  the  im- 
mediate stimulation  of  the  respiratory  central  organ.  (Rosenthal,  "  Die  Athem- 
bewegungen,"  etc.,  Berlin,  1862,  S.  4.)  My  own  experiments  were  published 
in  i86t. 

*  Pfluger,  op.  cit.,  S.  89. 

t  Ibid.,  S.  95. 


142  MEDULLA   IN    NORMAL   RESPIRATION 

blood  in  the  vessels  of  the  medulla  oblongata.  This  opinion 
has  been  entertained  by  certain  physiologists  on  theoretical 
grounds;  but  so  far  as  I  know,  it  had  not  been  sustained 
by  direct  experiment  prior  to  my  observations  in  1877. 

In  1877  I  made  a  series  of  experiments  which  seemed 
to  me  to  demonstrate  conclusively  that  the  sense  of  want 
of  air  is  due  to  a  deficiency  of  oxygen-carrying  blood  in 
the  medulla  oblongata.  The  details  of  these  experiments 
have  already  been  published,*  and  I  shall  here  give  merely 
a  summary  of  the  results. 

If  the  chest  of  a  dog  is  opened,  the  animal  being  under 
the  influence  of  ether,  and  if  artificial  respiration  is  effi- 
ciently maintained  the  animal  will  make  no  respiratory 
efforts  so  long  as  fresh  air  in  sufficient  quantity  is  supplied 
to  the  lungs.  This  is  an  old  experiment,  dating  from  the 
time  of  Robert  Hooke,  in  1664,  and  has  been  repeatedly 
verified. 

Air  still  being  supplied  in  adequate  quantity  to  the 
lungs,  if  the  aorta  is  tied  or  the  system  drained  of  blood,  the 
animal  will  make  violent  respiratory  efforts  under  the  in- 
fluence of  the  sense  of  want  of  air.  This  is  due  to  the  fact 
that  the  oxygen  can  not  get  to  the  system  or  to  some  part 
or  parts  of  the  system;  and  this  demonstration  w^as  made 
and  published  by  me  as  early  as  1861.  Similar  results  were 
obtained  by  Rosenthal  in  1862  and  by  Pfliiger  in  1868. 

In  1877  it  occurred  to  me  that  it  was  possible  to  ascer- 
tain by  experiment  whether  the  sense  of  want  of  air  was 
due  to  a  want  of  oxygen  in  the  general  system  or  in  some 
restricted  part.  It  being  so  w^ell  established  that  the  me- 
dulla oblongata  is  the  respiratory  nerve-centre,  I  was  nat- 
urally led  to  look  for  some  means  of  cutting  off  the  supply 
of  blood  from  this  part.  This  can  easily  be  done  by  tying 
the  innominate  artery  and  the  left  subclavian  artery  in  a 
dog,  in  this  animal  the  aorta  giving  off  from  the  arch  these 
two  vessels  which  are  the  only  sources  of  supply  of  blood 
to  the  head  and  the  anterior  extremities.  The  following 
experiment,  which  I  copy  from  my  article  published  in 
1877,  shows  the  effect  of  constricting  the  vessels  given 
off  from  the  arch  of  the  aorta.     This  experiment  is  a  type 

*  Flint,  "  Experiments  on  the  Effects  upon  Respiration  of  cutting  off  the 
Supply  of  Blood  from  the  Brain  and  the  Medulla  Oblongata." — "  New  York 
Medical  Journal,"  November,  1877,  vol,  xxvi.,  p.  449. 


MEDULLA    IN    NORMAL    RESPIRATION  143 

of  many  others  made  in  my  laboratory  and  in  public  dem- 
onstrations. 

September  30,  1877. — A  medium-sized,  full-grown  dog  was 
brought  completely  under  the  influence  of  ether.  The  trachea  was 
then  opened  and  connected  with  a  bellows  and  artificial  respiration 
was  maintained.  Over  the  valve  of  the  bellows  was  placed  a 
sponge,  which  was  saturated  with  ether  from  time  to  time,  so  that 
the  animal  was  kept  completely  anesthetized  during  the  experi- 
ment. The  air  in  the  bellows  was  also  changed  from  time  to  time 
by  pushing  up  the  valve  with  the  fingers  and  forcing  out  the  vitiated 
air.  The  chest  and  abdomen  were  then  laid  open  by  a  continuous 
incision  in  the  median  line,  and  the  ribs  were  bent  backward  and 
secured  with  a  strong  cord  tied  behind  the  back,  so  that  the  lungs 
and  heart  were  fully  exposed.  The  pericardium  was  then  cut 
away,  the  great  vessels  near  the  heart  were  isolated  and  loose  liga- 
tures were  thrown  around  the  trunk  of  the  innominate  artery,  the 
left  subclavian  artery,  the  descending  vena  cava,  the  descending 
portion  of  the  aorta,  and  the  ascending  vena  cava.*  In  this  way, 
I  was  prepared  to  constrict  the  several  vessels  at  will. 

When  these  preliminary  steps  had  been  completed,  the  animal 
being  entirely  under  the  influence  of  ether  and  artificial  respiration 
being  kept  up  efificiently,  there  were  absolutely  no  respiratory  ef- 
forts, and  the  diaphragm,  which  was  exposed,  was  quiescent. 

The  artificial  respiration  was  then  arrested.  In  forty-five  sec- 
onds the  animal  began  to  make  violent  respiratory  efTorts.  Artifi- 
cial respiration  was  then  resumed,  and  the  respiratory  efTorts  of 
the  animal  ceased.  When  the  artificial  respiration  was  arrested,  I 
first  noticed  a  movement  of  the  corners  of  the  mouth  at  regular 
intervals  and  then  the  mouth  was  widely  opened  and  the  diaphragm 
became  strongly  contracted,  also  at  regular  intervals.  The  time 
was  taken  at  the  first  violent  respiratory  effort. 

The  animal  being  quiet  and  making  no  efforts  at  respiration, 
the  innominate  artery,  the  left  subclavian  artery  and  the  descend- 
ing vena  cava  were  tied  almost  simultaneously,  artificial  respira- 
tion being  constantlv  and  efficiently  maintained.  In  two  minutes 
and  eight  seconds  the  animal  began  to  make  respiratory  efforts, 
which  continued  so  long  as  the  vessels  remained  constricted. 

The  ligatures  surrounding  the  vessels  mentioned  above  were 
loosened  five  minutes  and  twenty-two  seconds  after  they  had  been 
tied,  and  the  respiratory  efforts  of  the  animal  instantly  ceased. 
After  three  minutes,  artificial  respiration  was  stopped,  and  the  ani- 
mal began  to  make  respiratory  efforts  in  thirty-nine  and  a  half 
seconds,  Avhich  ceased  so  soon  as  artificial  respiration  was  re- 
sumed. 

The  descending  aorta  and  the  ascendinsf  vena  cava  in  the  chest 


*  In  the  dog,  the  aorta  gives  ofif  the  innominate  artery,  "  which  gives  off 
first  the  left  carotid,  and  then  divides  into  the  right  subclavian  and  right  ca- 
rotid "  (Foster,  "  Elementary  Practical  Physiology,"  London,  1876,  p.  13).  The 
left  subclavian  artery  arises  directly  from  the  aorta. 


144  MEDULLA    IN    NORMAL    RESPIRATION 

were  then  tied  simultaneously,  the  vessels  arising  from  the  arch 
of  the  aorta  being  free.  This  seemed  to  produce  no  effect,  and 
no  respiratory  efforts  were  made  by  the  animal  for  five  minutes. 
The  innominate  artery  and  the  left  subclavian  artery  were  then 
constricted,  the  aorta  and  ascending  vena  cava  remaining  tied. 
Respiratory  eft'orts  by  the  animal  began  in  one  minute  and  twenty- 
six  seconds,  although  artificial  respiration  was  maintained.  These 
efforts  ceased  when  the  ligatures  around  the  innominate  and  sub- 
clavian were  loosened. 

The  ligatures  were  then  removed  from  the  descending  aorta 
and  ascending  vena  cava,  and  the  innominate  and  left  subclavian 
arteries  were  constricted,  which  was  followed  by  respiratory  efforts 
after  one  minute  and  six  seconds.  These  efforts  ceased  when  the 
vessels  were  freed. 

The  innominate  artery  alone  was  then  constricted,  but  this 
seemed  to  produce  no  effect,  no  respiratory  efforts  being  made  by 
the  animal  for  five  minutes.  At  the  end  of  five  minutes  the  left 
subclavian  artery  was  constricted,  the  constriction  of  the  innomi- 
nate artery  being  maintained.  The  animal  began  to  make  respira- 
tory efforts  fifty-three  seconds  after  constriction  of  the  subclavian. 
These  efforts  ceased  on  loosening  the  ligatures. 

Artificial  respiration  was  then  stopped  and  the  animal  began 
to  make  respiratory  efforts  in  ten  seconds.  The  medulla  oblongata 
was  then  broken  up  and  the  experiment  was  concluded. 

In  this  experiment  I  had  the  aid  of  my  assistant,  Dr.  C.  F. 
Roberts,  and  Mr.  Caspar  Griswold,  an  advanced  laboratory  stu- 
dent. As  the  experiment  progressed,  it  was  ascertained  that  the 
vessels  could  be  effectually  constricted  by  making  traction  on  the 
ligatures  without  tying.  The  constriction  could  then  be  instantly 
removed.  It  was  also  ascertained  that  constriction  of  the  veins 
made  no  difference  in  the  phenomena  observed. 

The  general  result  of  all  my  experiments  made  on  the 
plan  of  the  one  just  detailed  was  that  invariably,  when  the 
innominate  and  the  left  subclavian  artery  were  tied,  the 
dogs  began  to  make  respiratory  efforts  in  a  little  more 
than  two  minutes  after  the  ligation,  but  the  animals  re- 
mained quiet  after  ligation  of  the  aorta  in  the  chest.  The 
respiratory  efforts  continued  so  long  as  the  vessels  going 
off  from  the  arch  of  the  aorta  remained  constricted,  and 
they  ceased  almost  immediately  when  the  Hgatures  were 
loosened.  During  all  of  my  observations  upon  the  effects 
of  tying  the  various  bloodvessels,  artificial  respiration  was 
kept  up  constantly  and  efficiently.  Under  the  view  which 
I  was  led  to  adopt  by  the  results  of  these  experiments — 
that  the  sense  of  want  of  air  was  due  to  a  deficiency  of 
oxygen-carrying  blood  in  the  medulla  oblongata — I  could 
not  be  certain  that  the  arterial  blood  was  entirely  shut  off 


MEDULLA    IN    NORMAL    RESPIRATION  145 

from  the  medulla  without  tying  the  innominate  and  the 
left  subclavian.  It  seemed  to  make  no  ditTerence  in  the 
results  of  the  experiments  whether  the  great  veins  were 
tied  or  left  free.  In  all  of  the  experiments  the  excitability 
of  the  medulla  was  repeatedly  shown  by  arresting  artificial 
respiration  from  time  to  time.  The  animals  began  to  make 
respiratory  efforts  in  thirty  to  forty-five  seconds  after  the 
arrest  of  artificial  respiration. 

The  results  of  my  experiments  show  that  when  the 
flow  of  oxygenated  blood  is  cut  off  from  the  parts  supplied 
by  the  vessels  given  off  from  the  arch  of  the  aorta  in  a 
living  animal,  the  sense  of  the  want  of  air  is  excited,  as  is 
evident  from  repeated  and  often  violent  respiratory  efforts, 
although  air  is  supplied  to  the  lungs.  Respiration  will 
continue  when  all  of  the  encephalic  ganglia,  with  the  ex- 
ception of  the  medulla  oblongata,  have  been  removed; 
and  it  is  well  known  that  this,  the  medulla,  is  the  sole 
respiratory  nervous  centre.  One  would  naturally  look, 
then,  to  influences  operating  upon  the  medulla  oblongata 
for  an  explanation  of  these  respiratory  efforts.  It  does  not 
seem  that  these  movements  can  be  clue  to  an  impression 
received  by  the  medulla  from  the  general  system  and  due 
to  want  of  oxygen;  for  when  the  descending  aorta  is  tied 
in  the  chest  no  respiratory  efforts  are  made.  The  move- 
ments, indeed,  occur  only  when  the  medulla  oblongata  is 
deprived  of  blood;  and  the  vessels  which  it  is  necessary  to 
tie  in  order  to  produce  this  result  involve  a  smaller  part 
of  the  general  systemic  circulation  than  when  the  descend- 
ing aorta  is  tied  in  the  chest. 

I  do  not  assume  that  the  view  just  enunciated  is  entirely 
novel;  but  so  far  as  I  know,  the  observations  made  in  1877 
were  the  first  to  sustain  such  a  view  by  positive  experi- 
mental evidence.  Upon  this  point  I  have  nothing  to  add 
to  what  I  have  already  stated  in  connection  with  the  fol- 
lowing quotations:  * 

"  The  first  respiratory  effort  of  the  foetus  is  thus  produced  by 
the  interruption  of  the  placental  respiration,  the  sudden  deficiency 
of  oxygen  and  increase  of  carbonic  acid  in  the  blood  (Schwartz). 
This  change  in  the  blood  needs  to  take  place  locally  only  in  the 
vessels  of  the  medulla  oblongata,  in  order  to  produce  this  effect; 
it  occurs,  for  example,  from  arrest  of  the  blood  in  these  vessels 

*  "New  York  Medical  Journal,"  November,  1877,  vol.  xxvi.,  p.  452. 
10 


146  MEDULLA    IN    NORMAL   RESPIRATION 

(by  ligature  of  the  carotid  arteries,  Kussmaul  and  Tenner,  Rosen- 
thal, or  by  closure  of  the  venous  currents  from  the  brain,  Hermann 
and  Escher),  by  which  their  blood  becomes  progressively  poorer  in 
oxygen  and  richer  in  carbonic  acid"  (Hermann,  "  Grundriss  der 
Physiologic  des  Menschen,"  Berlin,  1870,  S.  160). 

"If  the  supply  of  blood  be  cut  off  from  the  medulla  by  ligature 
of  the  blood-vessels  of  the  neck,  dyBi)noea  is  produced,  though  the 
operation  produces  no  change  in  the  blood  generally,  but  simply 
affects  the  respiratory  condition  of  the  medulla  itself,  by  cutting 
off  its  blood  supply,  the  immediate  result  of  which  is  an  accumula- 
tion of  carbonic  acid  and  a  paucity  of  available  oxygen  in  the  pro- 
toplasm of  the  nerve-cells  in  that  region."'  (Foster,  "  A  Text-Book 
of  Physiology,"  New  York,  1880,  p.  2,77-) 

These  quotations  from  Hermann  and  from  Foster  show  clearly 
that  their  idea  is  that  the  sense  of  want  of  air  is  due  to  deficiency 
of  oxygenated  blood  in  the  medulla  oblongata,  a  view  fully  sus- 
tained by  my  own  experiments.  The  observations  of  Kussmaul 
and  Tenner,  referred  to  by  Hermann,  were  made  with  reference 
to  the  cause  of  the  convulsions  which  so  often  occur  after  profuse 
and  sudden  hemorrhage.  They  are  to  be  found  in  the  elaborate 
memoir  by  Kussmaul  and  Tenner,  "  On  the  Nature  and  Origin  of 
Epileptiform  Convulsions  caused  by  Profuse  Bleeding,"  translated 
and  published  by  the  "  New  Sydenham  Society,"  in  1859.  Kuss- 
maul and  Tenner  made  a  large  number  of  experiments  on  rabbits 
and  horses,  in  which  they  observed  the  effects  of  tying  the  great 
vessels  given  off  from  the  arch  of  the  aorta.  They  noted,  after 
this  operation,  great  difficulty  in  respiration  and  violent  convul- 
sions. They  did  not,  however,  arrest  the  respiratory  movements 
of  the  animal  by  artificial  respiration,  thus  abolishing,  for  the  time, 
the  respiratory  sense,  and  then  note  the  effects  of  ligature  of  these 
vessels.  The  experiments  by  Rosenthal,  w^hich  are  referred  to,  are 
probably  those  contained  in  his  work  "  Die  Athembewegungen  und 
ihre  Beziehungen  zum  Nervus  Vagus,"  Berlin,  1862.  In  these 
experiments,  as  I  have  already  stated,  it  is  shown  that  the  respira- 
tory efforts  of  an  animal  can  be  abolished  by  forcing  atmospheric 
air  or  oxygen  in  large  quantities  through  the  lungs,  but  that  the 
sense  of  want  of  air  is  felt  when,  in  place  of  oxygen,  nitrogen 
or  hydrogen  is  employed,  by  this  means  removing  the  possibility  of 
an  irritation  from  carbonic  acid.  These  are  essentially  the  same 
as  the  observations  made  by  Pfliiger,  in  1868.  Rosenthal  states 
very  distinctly  that  the  sense  of  want  of  air  is  due  to  want  of 
oxygen-carrying  blood  in  the  medulla  oblongata ;  but  he  does  not 
actually  demonstrate  the  truth  of  this  proposition  by  experiments. 
The  statements  by  Hermann  and  Foster  are  apparently  based  upon 
the  experiments  of  Kussmaul  and  Tenner  and  of  Rosenthal ;  but 
I  must  nevertheless  claim  that  the  experiments  which  I  have  made 
upon  this  subject,  which  \v\\\  be  detailed  farther  on,  if  they  should 
be  confirmed,  afford  the  first  positive  proof  that  the  respiratory 
sense  may  be  excited  by  cutting  off  the  arterial  supply  from  the 
medulla.  There  is  nothing  which  I  can  find,  in  the  experiments 
of  Kussmaul  and  Tenner  or  of  Rosenthal,  which  actually  shows 


MEDULLA    IN    NORMAL    RESPIRATION  147 

that  the  sense  of  want  of  air  is  not  due  to  a  want  of  oxygen  in  the 
general  system. 

All  the  experiments  that  I  have  thus  far  referred  to 
have  of  necessity  involved  placing  the  animals  on  which 
the  observations  were  made  under  conditions  exceedingly 
unnatural.  It  can  not  be  assumed  that  after  the  chest  has 
been  opened  the  nerve-centres  possess  a  degree  of  sensi- 
bility and  a  power  of  action  entirely  normal.  Still  it  is 
not  easy  to  see  how  such  a  modification  of  the  natural  con- 
ditions can  be  avoided;  and  we  must  reason  as  best  we 
can  from  the  observations  that  have  been  made,  keeping 
in  view  the  experimental  conditions. 

It  is  certain  that  oxygen  may  be  artificially  supplied 
to  the  lungs  in  a  living  animal  so  efficiently  as  to  abolish 
for  the  time  the  sense  of  want  of  fresh  air,  to  satisfy  the 
requirements  of  the  system  for  oxygen  and  to  cause  all 
respiratory  efforts  on  the  part  of  the  animal  to  cease. 
When  artificial  respiration  is  arrested  and  the  blood  be- 
comes dark  in  the  arteries,  when  the  blood  is  drained  from 
the  system,  artificial  respiration  being  continued,  or  when 
oxygenated  blood  is  shut  off  from  the  medulla  oblongata, 
the  animal  makes  respiratory  efforts. 

Taking  into  consideration  all  the  experiments  bearing 
upon  this  point,  they  seem  to  show  beyond  question  that, 
under  the  conditions  indicated  above,  the  sense  of  want  of 
air.  the  stimulus  or  whatever  it  may  be  that  causes  the 
animal  to  make  respiratory  efforts  depends  tipon  some 
peculiar  condition  in  the  medulla  oblongata.  Still,  under 
the  conditions  mentioned;  that  is,  an  animal  under  the 
influence  of  ether  with  the  chest  opened  and  a  bellows  in 
the  trachea,  when  artificial  respiration  is  interrupted,  the 
respiratory  efforts  begin  in  thirty  to  forty-five  seconds. 
There  is  then  blood  in  the  medulla  oblongata,  contain- 
ing less  oxygen  and  more  carbonic  acid  than  normal 
arterial  blood  and  passing  through  the  capillaries  under 
great  pressure,  slowly  and  with  difficulty.  When,  on  the 
other  hand,  all  the  vessels  given  off  from  the  arch  of  the 
aorta  are  tied,  respiratory  efforts  begin  in  a  few  seconds 
more  than  two  minutes.  While  this  latter  experiment, 
taken  by  itself,  shows  that  shutting  off  the  oxygen-carrying 
fluid  from  the  medulla  oblongata  excites  the  sense  of  want 
of  air,  the  question  at  once  arises:  why,  when  the  vessels 


148  MEDULLA    IN    NORMAL    RESPIRATION 

which  supply  the  medulla  oblongata  are  filled  with  blood 
of  a  venous  character,  is  the  respiratory  sense  excited  so 
much  more  promptly  than  when  the  arteries  are  tied?  In 
other  words,  if  it  is  assumed  that  shutting  off  the  blood 
from  the  medulla  oblongata  will  excite  the  respiratory 
sense  by  cutting  off  the  supply  of  oxygen,  and  that  this 
will  induce  respiratory  efforts  in  about  two  minutes,  why 
does  the  simple  interruption  of  artificial  respiration,  which 
causes  blood  of  a  venous  character  to  go  to  the  medulla 
oblongata,  induce  respiratory  efforts  in  about  thirty  sec- 
onds? 

This  is  a  question  which  I  have  in  vain  attempted  to 
solve  to  my  entire  satisfaction.  When  artificial  respiration 
is  arrested  and  the  circulation  is  not  interfered  with  by 
the  tying  of  vessels,  the  venous  blood  passes  through  the 
lungs  and  back  to  the  left  side  of  the  heart  without  losing 
its  carbonic  acid  and  without  receiving  a  fresh  supply  of 
oxygen.  Under  these  conditions,  it  passes  through  the 
great  vessels  given  off  from  the  arch  of  the  aorta  to  the 
medulla  oblongata  as  well  as  to  other  parts;  and  the  main 
obstruction  to  the  blood-current,  which  produces  such  in- 
tense engorgement  of  the  cardiac  cavities,  exists  in  the 
systemic  capillaries.  It  is  fair  to  infer  that  the  capillaries 
of  the  medulla  are  engorged  as  well  as  others.  This  being 
the  condition,  it  is  logical  to  assume  that  the  oxidizing 
processes  which  normally  go  on  in  the  medulla  are  prompt- 
ly arrested;  and  it  may  also  be  assumed,  for  sake  of  argu- 
ment, that  this  arrest  of  oxidation  excites  the  sense  of  want 
of  air.  It  does  not  appear  how  any  experiment  can  be 
devised  in  which  the  venous  blood  could  be  admitted  in 
such  quantity  to  the  medulla,  at  the  same  time  maintain- 
ing the  normal  supply  of  oxygen  and  the  uninterrupted 
performance  of  normal  oxidation  in  this  particular  part. 

On  the  other  hand,  suppose  that  the  great  vessels  given 
off  from  the  arch  of  the  aorta  are  tied!  While  the  supply 
of  fresh  arterial  blood  is  thus  cut  off  from  the  medulla,  it 
is  well  known  that  the  contraction  of  the  vessels  beyond 
the  point  of  ligation,  which  is  slow  and  gradual,  as  is  char- 
acteristic of  non-striated  muscular  tissue,  will  still  force 
the  small  quantity  of  blood  which  these  vessels  contain 
through  the  medulla.  My  experiments  show  that  the  sup- 
ply of  arterial  blood  to  the  medulla  need  not  be  very  con- 


MEDULLA    IN    NORMAL    RESPIRATION  149 

siderable  in  order  to  satisfy  the  respiratory  sense.  Con- 
striction of  the  innominate  artery  alone  does  not  induce 
respiratory  efforts.  No  respiratory  efforts  are  made  when 
both  carotids  and  both  vertebral  arteries  are  constricted. 
These  efforts,  indeed,  occur  only  when  the  innominate  and 
the  left  subclavian  are  tied,  or  when  ligatures  are  applied 
to  both  carotids,  both  vertebrals  and  both  subclavians. 

Reasoning  from  these  facts  and  inferences,  the  follow- 
ing is  the  only  explanation  that  I  can  offer  of  the  rapid 
excitation  of  respiratory  efforts  by  simple  arrest  of  artificial 
respiration,  as  compared  with  the  effects  of  tying  the  ves- 
sels given  off  from  the  arch  of  the  aorta: 

When  artificial  respiration  is  interrupted,  the  normal 
oxidizing  process  in  the  medulla  oblongata  is  promptly 
arrested  and  respiratory  efforts  begin  in  thirty  to  forty- 
five  seconds.  When,  on  the  other  hand,  the  vessels  which 
supply  blood  to  the  medulla  are  tied,  the  contraction  of 
the  muscular  coats  of  the  vessels  beyond  the  points  of  liga- 
tion for  a  certain  time  forces  a  small  quantity  of  arterial 
blood  to  the  medulla,  and  it  is  only  w'hen  this  ceases  that 
the  want  of  oxygen  is  felt.  This  may  be  the  reason  why 
the  arrest  of  oxidation  in  the  medulla  is  later  when  the 
vessels  are  tied  than  when  artificial  respiration  is  inter- 
rupted. 

When  it  is  proved,  as  I  think  it  has  been  proved  con- 
clusively, that  an  animal,  after  the  respiratory  movements 
have  been  arrested  by  artificial  respiration,  will  make  re- 
spiratory efforts  when  the  supply  of  oxygen-carrying  blood 
is  shut  off  from  the  medulla  oblongata,  the  question  arises 
in  regard  to  the  application  of  this  experimental  fact  to 
the  mechanism  of  normal  respiration. 

Cause  of  the  Normal  Rhythmical  Movements  of 
Respiration. — The  normal  rhythmical  movements  of  res- 
piration are  excited  and  regulated  by  the  respiratory  nerve- 
centre  in  the  medulla  oblongata.  Under  ordinary  physi- 
ological conditions  the  exciting  cause  of  these  movements, 
whatever  it  may  be,  is  unconscious;  and  the  muscular  acts 
by  which  air  is  introduced  into  the  lungs  take  place  with- 
out efforts  of  the  will.  In  other  words,  the  movements 
of  ordinary  respiration  are  unconscious  and  involuntary. 
That  these  propositions  are  correct  has  been  proved  by 
experiments  that  are  perfectly  familiar  to  physiologists. 


I50  MEDULLA    IN    NORMAL    RESPIRATION 

When  all  the  nerve-centres  that  are  known  to  have  any 
relations  to  sensation  and  voluntary  movements  are  de- 
stroyed, the  medulla  oblongata  remaining  intact,  the 
rhythmical  movements  of  respiration  persist.  When  the 
medulla  oblongata  is  destroyed,  the  other  nerve-centres 
remaining  intact,  the  respiratory  movements  are  instantly 
arrested.  The  cause  of  this  arrest  of  respiratory  movements 
following  destruction  of  the  medulla  is  explained  by  the 
following  proposition: 

The  medulla  oblongata  contains  the  only  nerve-centre 
capable  of  appreciating  the  unconscious  sense  of  want  of 
air;  and  consequently,  when  this  centre  is  destroyed,  the 
sense  of  want  of  air  is  not  felt  and  no  true  respiratory  move- 
ments can  be  excited.  In  the  same  way,  when  oxygen  is 
freely  supplied  to  the  blood  of  a  living  animal  by  artificial 
means,  no  sense  of  want  of  air  exists  and  no  respiratory 
efiforts  occur.  In  the  foetus  in  utero,  so  long  as  oxygen 
is  supplied  to  the  blood  by  the  placenta,  no  respiratory 
efforts  are  made;  but  when  the  placental  circulation  is  in- 
terrupted, the  sense  of  want  of  air  is  developed  and  respira- 
tory efforts  occur.  This  may  take  place,  as  is  well  known, 
before  birth. 

My  experiments  published  in  1877  show  conclusively 
that  the  sense  of  want  of  air  is  developed  and  respiratory 
efforts  are  excited,  not  necessarily  by  a  possible  irritation 
due  to  the  circulation  of  venous  blood  in  the  medulla  ob- 
longata, but  by  cutting  off  from  the  medulla  the  supply 
of  oxygen.  This  occurs  when  the  respiratory  acts  have 
been  arrested  by  supplying  air  to  the  lungs  artificially. 

Under  ordinary  physiological  conditions,  the  heart- 
beats numbering  seventy-two  and  the  respirations  eighteen 
per  minute,  the  following  is  probably  the  mechanism  of  the 
flow  of  blood  through  the  capillaries  of  the  lungs  and  the 
vessels  of  the  medulla  oblongata: 

The  venous  blood  from  the  general  system  is  sent  to 
the  lungs  by  the  action  of  the  right  ventricle,  the  inter- 
mittent force  of  which  is  absorbed  by  the  elasticity  of  the 
pulmonary  artery  and  its  branches,  until  the  current  in 
the  pulmonary  capillaries  becomes  nearly  or  quite  steady 
and  continuous.  This  venous  blood  is  poor  or  deficient  in 
oxygen  and  rich  in  carbonic  acid.  As  it  passes  through 
the  lungs  it  gives  off  its  carbonic  acid  and  takes  up  oxygen. 


MEDULLA    IN    NORMAL   RESPIRATION  151 

In  the  pulmonary  vesicles  the  composition  of  the  air  is 
tolerably  uniform ;  that  is,  it.  contains  a  certain  proportion 
of  oxvgen  and  of  carbonic  acid.  But  at  the  same  time, 
the  air  in  the  pulmonary  cells  has  a  tendency  to  an  increase 
in  its  proportion  of  carbonic  acid  with  a  diminution  in  its 
oxygen;  for  the  venous  blood,  as  it  passes  through  the 
pulmonary  capillaries,  is  constantly  giving  off  carbonic  acid 
and  taking  up  oxygen.  This  tendency  to  a  diminution  in 
oxygen  and  an  increase  in  carbonic  acid  in  the  contents  of 
the  air  cells  progressively  increases  from  the  completion  of 
any  single  inspiratory  act  to  the  beginning  of  another. 
When,  however,  a  new  act  of  inspiration  occurs,  fresh  oxy- 
gen is  introduced  into  the  lungs,  which  supplies  the  place 
of  a  certain  quantity  of  carbonic  acid  thrown  off  by  the  pre- 
ceding expiration.  That  this  occurs  is  sufficiently  evident; 
and  it  is  illustrated  by  the  fact  that  when  expiration  is 
voluntarily  retarded,  the  expired  air  becomes  richer  in  car- 
bonic acid  and  poorer  in  oxygen  than  it  is  under  ordinary 
conditions. 

On  the  other  hand,  the  left  ventricle  is  sending  arterial 
blood  received  from  the  lungs  to  all  parts  of  the  system, 
including  the  medulla  oblongata.  The  elasticity  of  the 
aorta  and  of  its  branches  gradually  extinguishes  or  absorbs 
the  intermittent  force  of  the  heart,  so  that  the  blood  flows 
in  a  steady  and  continuous  stream  through  the  capillaries 
of  the  medulla.  But  as  the  tendency  of  the  air  in  the  pul- 
monary parenchyma  is  to  progressively  increase  its  pro- 
portionate quantity  of  carbonic  acid  and  to  diminish  its 
oxygen  between  two  inspiratory  acts,  the  tendency  of  the 
blood  coming  from  the  lungs  and  sent  by  the  left  ventricle 
to  the  medulla  oblongata  is  to  become  progressively  poorer 
in  oxygen.  After  about  four  revolutions  of  the  heart  (as- 
suming that  the  proportion  of  the  beats  of  the  heart  to 
the  respiratory  acts  is  as  four  to  one),  the  quantity  of 
oxygen  supplied  to  the  medulla  oblongata  has  become  so 
far  diminished  that  there  occurs  an  unconscious  sense  of 
want  of  air,  and  this  excites  a  new  inspiratory  act.  So  it 
is,  in  all  probabiHty,  that  the  normal,  rhythmical  acts  of 
inspiration  are  periodically  excited;  and  anything,  like  vio- 
lent muscular  exercise,  that  increases  the  activity  of  the 
consumption  of  oxygen,  of  necessity  increases  the  number 
of  respirations  per  minute. 


152  MEDULLA    IN    NORMAL   RESPIRATION 

In  my  opinion,  in  the  explanation  just  given  of  the 
cause  of  the  rhythmical  acts  of  respiration,  1  have  gone 
as  far  as  I  can,  in  the  present  condition  of  physiological 
knowledge,  without  becoming  involved  in  unprofitable 
speculation  and  in  a  discussion  of  propositions  not  justified 
by  established  facts.  All  that  can  at  present  be  positively 
assumed  to  be  true,  is  that  respiratory  movements  are  ex- 
cited by  a  want  of  oxygen  in  the  substance  of  the  medulla 
oblongata;  and  I  know  of  no  reasonable  theory  that  will 
explain  the  exact  mode  of  action  of  the  oxygen  of  the  blood 
upon  any  of  the  anatomical  elements  of  the  respiratory 
nerve-centre.  Still  it  may  not  be  uninteresting  to  refer 
to  an  explanation,  proposed  by  Pfliiger  *  in  1868  and  ad- 
vanced again  in  1878  by  Burkart,  the  substance  of  which 
is  contained  in  the  following  quotation: 

"  I.  The  ganglionic  cells  of  the  respiratory  centre  produce, 
when  there  is  a  deficiency  of  oxygen,  a  readily  oxidizable  sub- 
stance. 2.  This  substance  performs  its  function,  through  a  certain 
degree  of  production  and  accumulation,  as  a  stimulus  to  the  very 
cells  that  are  concerned  in  its  production.  3.  The  oxygen  of  the 
blood,  that  is  of  the  tissues,  operates  against  the  production  and 
accumulation,  and  consequently  the  stimulating  action  of  this  hypo- 
thetical substance  thus  restrained  or  removed.  The  capacity  of  the 
ganglionic  cells  to  produce,  in  a  greater  or  less  degree,  by  a  defi-- 
ciency  of  oxygen,  this  substance  which  excites  respiratory  move- 
ments, is  measured  by  the  vital  energy  of  the  cells,  as  far  as  this 
vital  energy,  or  better  the  energy  of  the  process  of  oxidation,  re- 
lates to  the  demand  for  oxygen  on  the  part  of  the  cells.  The  pro- 
duction of  the  hypothetical  substance  is  merely  the  vital  expression 
of  the  ganglionic  cells  of  the  respiratory  centre  through  a  deficiency 
in  oxygen,  and  it  ceases  with  the  life  of  the  cells  themselves."  f 

The  above  quotation,  which  it  was  somewhat  difficult 
to  render  into  idiomatic  English,  embodies  a  theory  which 
may  be  more  clearly  expressed  as  follows: 

The  nerve-cells  of  the  respiratory  centre  are  constantly 
producing  a  hypothetical  substance  which  acts  as  a  stimu- 
lus to  the  muscles  of  inspiration.  As  the  arterial  blood 
passes  through  the  capillaries  of  the  medulla,  its  oxygen 
combines  with  this  hypothetical  substance,  which  is  thus 

*  Pfliiger,  "  Ueber  die  Ursache  der  Athembewegungen,  sowie  der  Dyspnoe 
und  Apnoe." — "  Archiv  fur  die  gesammte  Physiologie,"  Bonn,  1868,  Bd.  i., 
S.  go. 

f  Burkart,  "  Studien  iiber  die  automatische  Thatigkeit  des  Athemcentrums 
und  iiber  die  Beziehungen  desselben  zum  Nervus  Vagus  und  anderen  Athem- 
nerven." — "  Archiv  filr  die  gesammte  Physiologie,"  Bonn,  1878,  Bd.  xvi.,  S.  436. 


MEDULLA   IN    NORMAL   RESPIRATION  153 

destroyed,  or  at  least  its  action  as  a  stimulus  to  the  mus- 
cles of  respiration  is  arrested.  The  quantity  of  this  sub- 
stance existing  in  the  cells  of  the  medulla  is  regulated  by 
the  supply  of  oxygen,  and  this  regulates  the  degree  of 
stimulation  of  the  respiratory  muscles.  The  production  of 
this  hypothetical  substance  is  a  manifestation  of  the  vital 
energy  of  the  cells,  and  this  production  ceases  with  the 
life  of  the  cells. 

The  theory  which  I  have  proposed  involves  the  follow- 
ing simple  propositions,  deduced  mainly  from  my  experi- 
ments published  in  1877: 

1.  When  the  respiratory  nerve-centre  is  fully  supplied 
with  oxygen  by  means  of  artificial  respiration,  this  centre 
gives  ofif  no  stimulus  to  the  muscles  of  inspiration  and  no 
respiratory  efiforts  occur. 

2.  When  there  is  a  deficiency  in  the  supply  of  oxygen 
to  the  respiratory  nerve-centre,  the  stimulus  which  gives 
rise  to  inspiratory  efforts  is  generated;  and  this  stimulus 
and  the  respiratory  efforts  which  follow  are  active  and 
vigorous  in  proportion  to  the  extent  and  duration  of  the 
deficiency  of  oxygen. 

3.  In  normal  respiration,  expiration  being  mainly  pas- 
sive, the  rhythm  and  extent  of  the  inspiratory  acts  are  regu- 
lated by  the  quantity  of  oxygen  supplied  to  the  medulla 
oblongata.  Thus,  when  there  is  a  tendency  to  a  deficiency 
of  oxygen  in  the  arterial  blood,  as  its  proportion  must 
gradually  and  progressively  diminish  from  the  end  of  one 
inspiratory  act  to  the  beginning  of  another,  this  need  of 
oxygen,  or  unconscious  sense  of  want  of  air,  induces  a 
stimulus  which  leads  to  the  introduction  of  fresh  air  into 
the  lungs. 

4.  As  oxygen  can  get  to  the  medulla  oblongata  only 
through  the  blood,  serious  disturbances  of  the  circulation 
are  always  attended  with  an  exaggeration  of  the  respira- 
tory sense,  although  the  lungs  may  be  freely  supplied  with 
pure  air. 

The  theory  of  Burkart  involves  the  assumption  of  the 
existence  of  a  "  readily  oxidizable  substance  "  which  the 
cells  of  the  medulla  oblongata  have  a  constant  tendency 
to  produce  and  which  the  oxygen  of  the  blood  has  a  con- 
stant tendency  to  destroy.  Burkart  assumes  that  this  hy- 
pothetical substance  acts  as  a  stimulus  to  the  muscles  of 


154  MEDULLA    IN    NORMAL    RESPIRATION 

inspiration;  I  contend  that  it  is  not  logical  to  go  farther 
in  an  explanation  of  the  generation  of  the  respiratory  stim- 
ulus than  to  state  the  fact,  which  I  have  demonstrated 
experimentally,  that  the  sense  of  want  of  air,  be  it  uncon- 
scious, as  in  ordinary  respiration,  or  conscious,  as  it  is  when 
it  becomes  a  sense  of  sufifocation,  is  due  to  a  deficiency 
in  the  supply  of  oxygen  to  the  respiratory  nerve-centre. 

Cause  of  the  Conscious  and  Exaggerated  Move- 
ments OF  Respiration  in  Dyspncea. — In  ordinary  respi- 
ration, the  sense  of  want  of  air,  which  is  the  starting  point 
of  the  stimulus  that  gives  rise  to  the  respiratory  acts,  is 
entirely  unconscious,  and  the  acts  of  inspiration  are  in- 
voluntary and  automatic.  Even  when  there  is  a  slight 
deficiency  in  the  proper  aeration  of  the  blood,  as  occurs 
from  the  vitiated  atmosphere  of  a  crowded  room,  one  ex- 
periences merely  an  indefinite  sense  of  oppression,  and  the 
respiratory  movements  are  still  of  the  same  involuntary 
character.  But  when  there  occurs  any  serious  interference 
with  the  passage  of  fresh  air  to  the  pulmonary  vesicles 
or  an  obstruction  to  the  flow  of  arterial  blood  to  the  me- 
dulla oblongata,  as  in  certain  pulmonary  and  cardiac  dis- 
eases, the  sense  of  want  of  air  is  exaggerated  until  it  be- 
comes a  consciousness  of  pulmonary  oppression  or  impend- 
ing suffocation.  Under  such  conditions  many  muscles  that 
are  not  usually  brought  into  action  in  inspiration  are  used, 
partly  by  an  effort  of  the  will.  This  is  simply  an  exaltation 
and  extension  of  the  normal  respiratory  sense,  so  that  it 
reaches  the  true  centres  of  sensation,  causing  a  voluntary 
increase  in  the  number  and  extent  of  the  inspiratory  acts. 
The  sense  of  suffocation,  indeed,  differs  from  the  normal 
unconscious  respiratory  sense  merely  in  degree  and  in  the 
fact  that  the  former  operates  on  the  centres  of  ordinary 
sensation  through  sensory  nerves,  while  the  latter  is  con- 
fined to  the  medulla  oblongata.  Having  once  ascertained 
definitely  the  cause  of  the  normal  sense  of  want  of  air,  one 
can  readily  understand  how  an  exaggeration  of  the  condi- 
tions which  give  rise  to  the  natural  automatic  movements 
of  respiration  may  produce  those  sensations  which  attend 
the  various  degrees  of  suffocation.  As  more  remote  con- 
sequences of  asphyxia,  there  occur  insensibility,  an  arrest 
of  the  circulation  by  engorgement  of  the  heart  and  finally 
the  sensibility  of  the  medulla  oblongata  disappears.     As 


MEDULLA    IN    NORMAL   RESPIRATION  155 

a  general  rule,  when  the  action  of  the  heart  has  ceased  from 
asphyxia,  even  the  most  efficient  artificial  respiration  fails 
to  restore  the  respiratory  function,  for  the  reason  that  it  is 
only  by  the  action  of  the  heart  that  blood  can  be  sent  to 
the  medulla.  While,  however,  the  heart  continues  to  act, 
although  its  contractions  may  be  very  feeble,  it  is  within 
the  limits  of  possibiHty  to  revive  the  functions  of  the  me- 
dulla by  artificial  respiration. 

There  are  certain  agents  which  seem  to  affect  the  me- 
dulla directly,  such  as  narcotics  and  anesthetics.  In  poi- 
soning by  opium  the  frequency  of  the  respiratory  acts  is 
diminished  and  they  may  be  arrested.  All  experimenters 
must  have  frequently  observed  arrest  of  respiration  by  the 
administration  of  anaesthetics  to  animals.  In  such  in- 
stances, if  the  heart  continues  to  beat,  it  generally  is  pos- 
sible to  revive  the  respiratory  function  by  artificial  insuffla- 
tion of  the  lungs.  In  most  cases  of  suspended  respiratory 
action  from  any  temporary  cause,  although  electricity,  sud- 
den and  active  stimulation  of  the  surface,  etc.,  may  aid  in 
restoration,  the  main  reliance  should  be  upon  persistent  and 
efficient  artificial  respiration. 

Cause  of  the  First  Respiratory  Act  after  Birth 
AND  OF  Respiratory  Efforts  in  Utero. — No  one 
doubts,  at  the  present  day,  that  the  blood  from  the  placenta 
furnishes  to  the  foetus  in  utero  all  the  oxygen  demanded 
for  the  function  of  respiration;  and  it  is  unnecessary  to 
cite  authorities  to  show  that  the  blood  of  the  umbilical 
vein  contains  oxygen,  as  this  fact  has  long  since  been  es- 
tablished. If  the  uterus  of  an  animal  far  advanced  in  ges- 
tation is  opened,  an  experiment  which  I  have  frequently 
made  on  cats  and  dogs,  the  foetuses  for  a  time  will  make 
no  respiratory  efforts;  but  compression  of  the  umbilical 
vessels  of  one  will  cause  it  to  make  very  violent  move- 
ments of  inspiration,  while  the  others  will  remain  quiet 
so  long  as  the  placental  circulation  is  not  interrupted.  The 
umbilical  vein  carries  its  blood  to  the  vena  cava  ascendens, 
thence  to  the  left  side  of  the  heart  through  the  foramen 
ovale,  and  thence  to  the  upper  extremities  and  head,  in- 
cluding, of  course,  the  medulla  oblongata.  Thus  the  blood 
that  is  most  highly  oxygenated  is  supplied  to  the  medulla; 
and  the  aorta  below  the  arch  receives,  through  the  ductus 
arteriosus,  the  blood  from  the  right  ventricle,  which  con- 


156  MEDULLA    IN    NORMAL    RESPIRATION 

tains  a  much  smaller  quantity  of  oxygen  than  the  blood 
distributed  through  the  vessels  given  off  above.  Cutting 
off  the  flow^  of  blood  from  the  placenta  is  almost  equivalent, 
therefore,  to  tying  the  vessels  of  the  arch  of  the  aorta. 
When  this  is  done,  the  flow  of  oxygenated  blood  to  the 
medulla  is  arrested;  and  there  follows  a  sense  of  want  of 
air  which  induces  a  stimulus  that  is  sent  to  the  muscles 
of  inspiration.  Air  is  then  for  the  first  time  taken  into 
the  lungs,  and  the  conditions  of  the  circulation  are  changed. 
The  lungs  are  now  distended  with  air,  and  the  pulmonary 
vessels  are  dilated,  so  that  the  right  ventricle  supplies  the 
pulmonary  capillaries,  instead  of  sending  the  venous  blood, 
as  before,  in  greatest  part  through  the  ductus  arteriosus. 
The  pulmonary  circulation  being  thus  established,  the  con- 
ditions rapidly  assume  the  character  observed  in  the  adult. 
It  is  evident,  from  the  experiments  already  noted  show- 
ing the  effects  of  compression  of  the  umbilical  vessels,  that 
an  abnormal  condition  in  utero,  in  which  there  is  serious 
interference  with  the  placental  circulation,  may  induce  in- 
spiratory efforts  in  the  foetus,  and  that  the  liquor  amnii  may 
thus  find  its  way  into  the  air-passages. 

ARE  THE  NORMAL  RESPIRATORY  MOVEMENTS  EITHER  EN- 
TIRELY OR  IN  PART  REFLEX,  IN  THE  SENSE  IN  WHICH 
THE  TERM  REFLEX  IS  ORDINARILY  UNDERSTOOD  BY 
PHYSIOLOGISTS? 

This  question  is  one  which  naturally  arises  as  a  logical 
sequence  of  the  experiments  I  have  described  and  of  the 
deductions  that  I  have  drawn  from  the  ascertained  facts. 
The  most  important  of  these  facts  is  the  following:  When 
the  medulla  oblongata  is  freely  supplied  with  oxygen-car- 
rying blood  in  a  living  animal,  this  being  effected  by  arti- 
ficial insufflation  of  the  lungs,  there  are  no  inspiratory 
efforts.  The  animal  makes  respiratory  efforts  as  the  supply 
of  oxygen  to  the  medulla  diminishes;  and  the  want  of  oxy- 
gen alone  is  capable  of  inducing  the  stimulus  to  the  mus- 
cles which  gives  rise  to  the  efforts  to  introduce  air  into 
the  lungs.  It  is  evident  that  the  stimulus,  under  these 
experimental  conditions,  which  was  formerly  thought  to 
be  reflex  and  produced  by  a  certain  impression  conveyed 
to  the  medulla  by  centripetal  nerves,  really  takes  its  origin 


MEDULLA   IN    NORMAL    RESPIRATION  157 

in  the  medulla  itself;  that  the  respiratory  sense,  so  called, 
is  due  to  some  alteration  in  the  conditions  of  the  medulla, 
which  depends  upon  the  supply  of  oxygen-carrying  blood; 
and  finally,  that  this  alteration  does  not  of  necessity  in- 
volve any  impression  received  through  afferent  nerves. 
Viewed  in  this  way,  when  a  living  animal,  in  which  the 
respiratory  movements  have  been  for  the  time  arrested  by 
artificial  insufflation  of  the  lungs,  makes  inspiratory  efforts 
following  the  operation  of  shutting  off  the  blood-supply 
from  the  medulla,  the  stimulus  which  gives  rise  to  these 
efforts  can  not  properly  be  called  reflex. 

I  shall  leave  out  of  the  question  under  consideration 
various  modifications  of  the  respiratory  acts,  such  as 
coughing,  sneezing,  etc.,  and  the  influence  of  certain  un- 
usual impressions  made  upon  the  surface,  as  by  a  cold 
douche,  restricting  the  discussion  to  the  normal  respiratory 
movements. 

It  is  well  known  that  a  relatively  strong  electric  current 
applied  to  the  pneumogastric  nerves  in  the  neck  or  to  cer- 
tain branches  of  the  pneumogastrics,  the  superior  and  the 
inferior  laryngeals,  will  instantly  arrest  respiration.  This 
action  is  reflex,  as  is  shown  by  the  fact  that  stimulation 
of  the  central  ends  of  the  divided  nerves  influences  respira- 
tion, while  the  stimulus  applied  to  the  peripheral  ends  has 
no  effect.  The  effect  of  powerful  electric  stimulation  of 
the  pneumogastrics  and  of  certain  of  their  branches  is 
marked  and  constant;  at  the  same  time,  stimulation  of 
some  of  the  nerves  of  general  sensibility  has  been  observed 
to  arrest  respiratory  movements,  although  this  result  is 
not  invariable.  When  the  respiratory  movements  are  com- 
pletely arrested  by  faradization  of  the  pneumogastrics,  it 
is  always  the  same  for  the  general  movements  of  the  ani- 
mal, which  remains  motionless.*  On  the  other  hand,  "  a 
feeble  excitation  accelerates  the  respiration;  a  more  power- 
ful excitation  retards  it;  a  very  powerful  excitation  arrests 
it.  These  words  '  feeble  '  and  '  powerful '  having,  it  is  un- 
derstood, only  a  relative  sense  for  any  one  animal,  and 
tmder  certain  conditions:  what  is  feeble  for  one  would  be 
powerful  for  another,  etc."  f 

*  Bert,  "  Legons  sur  la  physiologic  comparee  de  la  respiration,"  Paris,  1870, 
p.  490. 

t  Bert,  loc.  cit. 


158  MEDULLA    IN    NORMAL    RESPIRATION 

So  far  as  these  experimental  facts  can  be  applied  to  the 
physiology  of  ordinary  respiration,  it  seems  that  the  nerves, 
the  action  of  which  is  brought  into  play  under  physiological 
conditions,  must  be  mainly  if  not  exclusively  the  pneumo- 
gastrics.  These  nerves  have  their  origin  at  the  medulla 
oblongata,  which  undoubtedly  contains  the  sole  respiratory 
nerve-centre;  they  are  distributed  to  the  entire  respiratory 
apparatus  from  the  larynx  to  the  deepest  parts  of  the  lungs; 
they  are  the  only  nerves  belonging  to  the  cerebro-spinal 
system  that  are  distributed  to  the  larynx,  trachea,  bronchia 
and  the  pulmonary  parenchyma;  while  they  are  not  distrib- 
uted to  the  respiratory  muscles,  except  the  intrinsic  mus- 
cles of  the  larynx,  they  are  capable,  by  reflex  action,  of 
exerting  a  very  marked  influence  over  the  respiratory 
movements.  In  discussing,  then,  the  question  of  reflex 
nervous  action  in  normal  respiration,  the  argument  may 
properly  be  confined  to  the  pneumogastrics. 

The  curious  and  interesting  respiratory  phenomena  ob- 
served in  living  animals  after  section  of  both  pneumogas- 
trics are  very  important.  When  both  pneumogastrics  are 
divided  in  the  neck,  the  excitation  directly  produced  by 
their  section  momentarily  accelerates  the  respiratory  move- 
ments. In  very  young  animals,  in  which  the  cartilages  of 
the  larynx  are  comparatively  soft  and  pliable,  the  paral- 
ysis of  the  inferior  laryngeal  nerves,  which  preside  over  the 
respiratory  movements  of  the  glottis,  often  produces  speedy 
suffocation  from  closure  of  the  glottis  during  the  inspira- 
tory act ;  but  in  most  adult  animals  the  walls  of  the  larynx 
are  sufficiently  rigid  to  enable  the  acts  of  inspiration  to  be 
carried  on  without  serious  obstruction.  In  such  animals, 
for  a  few  seconds,  the  number  of  respiratory  acts  may  be 
increased;  but  so  soon  as  they  become  tranquil,  the  num- 
ber is  very  much  diminished  and  the  movements  change 
their  character.  The  inspiratory  acts  become  unusually 
profound  and  are  attended  with  excessive  dilatation  of 
the  thorax.  Under  these  conditions  I  have  seen  the  num- 
ber of  respirations  fall  from  sixteen  or  eighteen  to  four 
per  minute. 

In  discussing  the  possible  reflex  influences  upon  the 
normal  respiratory  movements  which  may  operate  through 
the  pneumogastrics,  I  shall  make  use  of  a  very  interesting 
suggestion  made  by  Rosenbach,  in  1878.     In  a  brief  note 


MEDULLA    IN    NORMAL   RESPIRATION  159 

upon  the  "  Influence  of  Stimulation  of  the  Vagus  upon 
Respiration,"  Rosenbach  proposes  the  theory  that  this 
nerve  (the  vagus)  is  the  vasomotor  nerve  of  the  medulla 
oblongata,  and  that  it  contains  fibres  which  contract,  and 
fibres  which  dilate  the  bloodvessels.  This  idea  is  presented 
by  Rosenbach  simply  as  an  hypothesis,  which  he  "  hopes 
later  to  be  able  to  establish  by  experiments."  * 

I  may  now  state,  in  continuing  my  argument,  the  fol- 
lowing propositions,  all  of  which,  except  the  last,  I  assume 
to  be  facts  that  have  been  established  experimentally: 

I.  A  deficiency  in  the  quantity  of  oxygen  supplied  to 
the  medulla  oblongata  through  the  arterial  blood  circu- 
lating in  its  substance  will  of  itself  give  rise  to  a  stimula- 
tion of  the  muscles  concerned  in  the  act  of  inspiration. 

II.  A  relatively  feeble  electric  stimulation  of  the  pneu- 
mogastric  nerves  increases  the  frec}uency  of  the  inspiratory 
acts;  a  stronger  stimulation  may  diminish  their  frequency; 
and  a  very  powerful  stimulation  arrests  the  respiratory 
movements.  The  action  in  these  instances  is  reflex  and 
not  direct. 

III.  Section  of  both  pneumogastric  nerves  in  the  neck, 
in  most  adult  animals,  very  greatly  diminishes  the  fre- 
quency of  the  respiratory  acts. 

IV.  The  pneumogastric  nerves  possibly  contain  vaso- 
motor filaments  that  are  capable  of  regulating  and  modi- 
fying the  supply  of  blood  to  the  vessels  of  the  medulla 
oblongata. 

If  these  propositions  are  taken  as  the  basis  of  a  theory 
of  the  mechanism  of  normal  respiration,  the  following  seem 
to  be  the  natural  and  logical  conclusions  to  be  drawn  from 
them: 

I.  When  the  action  of  the  medulla  oblongata  is  re- 
moved from  the  influence  of  the  pneumogastric  nerves,  as 
it  is  after  division  of  both  of  these  nerves  in  the  neck,  air 
is  taken  into  the  lungs  when  the  deficiency  of  oxygen  in 
the  medulla  has  reached  the  point  at  which  the  respiratory 
sense  necessarily  generates  the  stimulus  sent  to  the  inspira- 
tory muscles.  This  action  is  in  no  sense  reflex,  and  it  de- 
pends entirely  upon  the  development,  de  novo,  of  a  stimu- 

*  Rosenbach,   "  Notiz  liber   den    Einfluss  der  Vagusreizung  aiif  die  Ath- 
miing." — "  Archiv  fiir  die  gesammte  Physiologic,"  Bonn,  1878,  Bd.  xvi.,  S.  503. 


i6o  MEDULLA    IN    NORMAL   RESPIRATION 

lation  or  an  irritation  in  the  medulla  itself.  Under  these 
conditions  the  acts  of  inspiration  are  abnormally  infrequent 
and  they  become  excessively  prolonged  and  profound. 

n.  In  normal  respiration,  however,  it  is  certain  that  im- 
portant reflex  influences  operate  upon  the  medulla  ob- 
longata through  the  pneumogastric  nerves.  While  there 
can  be  no  doubt  that  the  stimulus  which  gives  rise  to  in- 
spiratory efforts  is  due  purely  and  simply  to  want  of  oxy- 
gen in  the  medulla,  in  order  that  this  stimulus  shall  operate 
in  accordance  with  the  requirements  of  the  system  for 
oxygen,  producing  normally  sixteen  to  twenty  inspirations 
per  minute  and  varying  the  number  of  these  movements 
with  different  physiological  conditions  of  the  organism, 
depending  upon  muscular  exercise,  etc.,  it  is  necessary  that 
the  respiratory  acts  should  be  regulated  through  the  nerv- 
ous system.  Inasmuch  as  the  respiratory  acts  involve  the 
contraction  of  striated  muscular  fibres,  it  would  be  ex- 
pected that  the  nerves  which  regulate  them  should  belong 
to  the  cerebro-spinal  system.  In  studying  experiment- 
ally the  influence  of  various  nerves  on  the  respiratory 
movements,  it  is  found  that  the  pneumogastrics,  which 
arise  from  the  medulla  and  are  distributed  largely  to  the 
respiratory  apparatus,  are  closely  connected  with  certain 
artificially-induced  modifications  of  respiratory  action.  By 
applying  to  these  nerves  electric  stimulation  of  different 
degrees  of  intensity,  the  respiratory  movements  may  be  in- 
creased or  diminished  in  frequency  or  they  may  be  arrested, 
and  these  phenomena  are  always  reflex. 

III.  Section  of  both  pneumogastric  nerves  seems  to  re- 
move the  medulla  oblongata,  so  far  as  its  action  as  a  re- 
spiratory nervous  centre  is  concerned,  from  the  reflex  action 
of  the  nervous  system;  and  the  respiratory  acts  then  be- 
come so  far  diminished  in  frequency  and  are  so  laboured 
as  to  produce  serious  pulmonary  lesions.  It  is  probable 
that  death  occurs  in  a  few  days  after  this  operation,  not 
alone  from  abnormal  respiratory  action  but  from  a  sus- 
pension of  other  important  functions  which  the  pneumo- 
gastrics have  to  perform.  It  is  possible,  also,  that  some 
of  the  phenomena  that  are  observed  in  narcotic  poison- 
ing, notably  the  great  diminution  in  the  number  of  respira- 
tory movements,  are  due  to  an  interference  wdth  the  re- 
spiratory functions  of  the  pneumogastrics. 


MEDULLA    IN    NORMAL   RESPIRATION  i6i 

The  precise  mechanism  of  the  action  of  the  pneumogas- 
trics  in  normal  respiration  and  the  exact  seat  and  character 
of  the  impressions  which  serve  as  the  starting  point  in  the 
reflex  phenomena  observed,  it  is  difficult  to  describe  within 
the  limits  of  ascertained  facts.  If  the  theory  advanced  by 
Rosenbach  is  accepted;  viz.,  that  the  pneumogastrics  con- 
tain vasomotor  filaments  which  regulate  the  quantity  of 
blood  passing  through  the  medulla  oblongata,  the  mechan- 
ism of  the  action  which  takes  place  in  the  respiratory 
nerve-centre  is  readily  understood;  but  the  seat  and  the 
exact  nature  of  the  impression  which  gives  rise  to  these  re- 
flex changes  in  the  calibre  of  the  vessels  are  still  a  matter 
of  speculation  and  conjecture.  So  far  as  muscular  action 
in  tranquil  respiration  is  concerned,  it  is  necessary  to  con- 
sider only  the  acts  of  inspiration,  for  expiration  is  produced 
mainly  by  the  passive  reaction  of  the  walls  of  the  thorax 
and  by  the  resiliency  of  the  elastic  pulmonary  parenchyma 
succeeding  the  action  of  the  muscles  which  enlarge  the 
chest  and  inflate  the  lungs. 

Finally,  the  respiratory  sense,  "  besoin  de  respirer," 
sense  of  want  of  air,  or  the  stimulus  which  gives  rise  to  in- 
spiratory efforts,  is  due  purely  and  simply  to  a  deficiency 
in  oxygen  in  the  medulla  oblongata,  in  which  is  contained 
the  sole  respiratory  nerve-centre.  The  frequency  and  the 
extent  of  the  normal  inspiratory  movements  are  regu- 
lated and  accommodated  to  the  physiological  requirements 
of  the  system  by  reflex  action  operating  through  the  pneu- 
mogastric  nerves. 

In  this  article  I  have  endeavored  to  set  forth  the  na- 
ture and  the  physiological  bearings  of  my  experiments, 
published  in  1877,  showing  that  the  sense  of  want  of  air  is 
due  primarily  to  a  deficiency  of  oxygen  in  the  medulla 
oblongata.  I  have  attempted,  also,  to  show  how  the  oper- 
ation of  the  stimulus  to  the  inspiratory  muscles,  which  is 
due  to  this  deficiency  of  oxygen  in  the  medulla,  is  regu- 
lated, in  normal  respiration,  by  reflex  action  through  the 
pneumogastric  nerves.  Physiologists  are  now  well  ac- 
quainted with  the  action  of  the  pneumogastrics  in  connec- 
tion with  the  circulation,  the  action  of  the  stomach  and 
intestines  and  certain  functions  of  the  liver;  but  the  action 
of  these  nerves  in  normal  respiration  and  the  causes  of  the 
II 


i62  MEDULLA    IN    NORMAL    RESPIRATION 

respiratory  phenomena  following  their  stimulation  and 
their  section  have  heretofore  been  obscure.  I  venture  to 
hope  that  my  discussion  of  the  reiiex  function  of  the  pneu- 
mogastrics  in  connection  with  the  respiratory  movements 
has^thrown  some  light  upon  questions  which  have  not  been 
satisfactorily  answered  by  physiologists. 


IX 

EXPERIMENTAL  RESEARCHES  INTO  A  NEW 
EXCRETORY  FUNCTION  OF  THE  LIVER; 
CONSISTING  IN  THE  REMOVAL  OF  CHO- 
LESTERIN  FROM  THE  BLOOD,  AND  ITS 
DISCHARGE  FROM  THE  BODY  IN  THE  FORM 
OF  STERCORIN.  (THE  SEROLINE  OF  BOU- 
DET.)* 

ILLUSTRATED   BY   THREE   PLATES   CONTAINING   FIFTEEN 

FIGURES 

Published  in  the  "American  Journal  of  the  Medical  Sciences" 
for  October,  1862. 

"  La  cholesterine  du  sang  est  elle  un  de  ces  produits  destines 
a  etre  expulses  de  I'economie,  et,  par  consequent,  depotirvus  d'ac- 
tion  immediate  sur  I'economie  elle  meme  ?  Sa  destination  est  tout 
a  fait  inconnue."  "  Traite  de  physiologie,"  par  F.  A.  Longet. 
Paris,    1861.     Tome   i.,   p.   488. 

This  sentence,  which  is  taken  from  the  most  elaborate 
treatise  on  physiolog)^  in  any  language,  published  at  the 
centre  of  physiological  science,  in  1861,  expresses  the  state 
of  our  knowledge  in  regard  to  the  function  of  choles- 
terin.  Cholesterin  was  discovered  in  1782,  by  Poulletier 
de  la  Salle,  in  biliary  calculi,  and  was  detected  upwards  of 
thirty  years  ago  in  the  blood  by  Denis;  but  since  then,  with 
the  exception  of  researches  of  a  purely  chemical  nature 
into  its  properties,  our  knowledge  in  regard  to  it  has 
not  advanced.  Its  chemical  history  even,  is  far  from  per- 
fect; while  its  physiological  history  is  unknown.     In  1833 

*  A  French  translation  of  this  essay  was  published  in  Paris  in  l868,  and  in 
i86g  received  an  "honorable  mention"  with  a  "recompense"  of  1,500  francs 
from  the  Institute  of  France  (Academie  des  Sciences),  Concours^  Monthyon 
(Medecine  et  Chirurgie),  being  second  to  the  essay  of  Villemin  (Etudes  sur  la 
tuberculose,  preuves  rationnelles  et  experimentales  de  sa  specificite  et  de  son 
inoculabilite),  which  work  received  the  Monthyon  prize  for  that  year. 

163 


i64  NEW    FUNCTION   OF   THE    LIVER 

Boiidet  discovered  a  substance  in  the  blood  which  he  called 
"  seroline  ";  a  principle  having  many  characters  in  com- 
mon with  cholesterin,  but  heretofore  interesting  merely  as 
a  curious  proximate  principle,  found  in  excessively  minute 
quantities  in  the  serum  of  the  blood  only  (whence  its  name); 
too  minute,  indeed,  for  ultimate  analysis.  Its  function  was 
as  obscure  as  that  of  cholesterin.  In  examining  the  litera- 
ture of  these  two  substances,  I  find  that  cholesterin  is 
frequently  not  treated  of  in  systematic  works  on  physiolo- 
gy. Serolin  is  seldom  even  mentioned.  Their  function 
has  been  so  obscure  and  apparently  so  unimportant,  that 
theories  in  regard  to  it  have  not  been  advanced;  and 
the  highest  chemical  authorities,  in  speaking  of  their  office 
in  the  economy,  simply  say  of  one,  as  of  the  other,  that  it 
is  unknown.  In  the  "  Chimie  ana1<Dmique,"  by  Robin  and 
Verdeil,  I  find  cholesterin  summed  up  in  these  words: 

"  Le  role  physiologique  qu'elle  remplit  dans  I'economie  est 
egalement  inconnu." 

Of  serolin,  the  same  authors  say: 

"  On  ne  sait  pas  comment  se  forme  la  seroline,  ni  quel  est  son 
role  physiologique." 

Though  the  physiology  of  these  substances  is  thus  ob- 
scure, though  chemistry  has  thus  far  done  but  little  for 
their  history,  and  physiology  nothing,  certain  facts  with 
relation  to  them  would  seem  to  indicate  that  they  are  not 
unimportant  in  the  economy.  Cholesterin  is  found  in  the 
blood,  bile,  liver,  nervous  matter,  crystalline  lens,  meconi- 
um (not  in  the  feces,  as  incorrectly  stated  by  authors), 
beside  in  a  number  of  morbid  products.  It  is  found  in 
these  situations  constantly;  it  appears  in  the  blood  as  soon 
as  that  fluid  is  found,  and  continues  to  the  end  of  life.  Its 
quantity  in  the  blood  is  increased  in  certain  diseased  condi- 
tions and  diminished  in  others.  Serolin  has  been  said  to 
exist  constantly  in  the  blood,  though,  till  now,  it  has  never 
been  discovered  in  any  other  situation.  It,  like  cholesterin, 
is  a  constant  principle,  they  having  many  chemical  charac- 
ters in  common.  Their  function  is  definite;  it  is  important; 
and,  if  the  writer  does  not  exaggerate  this  importance  in 
the  enthusiasm  of  exploring  a  hitherto  absolutely  uncul- 
tivated field,  a  knowledge  of  the  functions  of  these  sub- 
stances will  be  of  incalculable  value  to  the  practical  physi- 


NEW    FUNXTION   OF  THE    LIVER  165 

cian;  and  the  path  thus  opened  by  physiology  will  lead  to 
a  great  field  for  pathological  inquiry.  What  the  discovery 
of  the  function  of  urea  has  done  for  diseases  which  now 
come  under  the  head  of  uremia,  the  discovery  of  the  func- 
tion of  cholesterin  may  do  for  the  obscure  diseases  which 
may  hereafter  be  classed  under  the  head  of  cholesteremia. 

It  is  not  surprising  that  the  function  of  substances — 
which  have  been  isolated  with  great  difficulty,  which  have 
never  been  found  in  any  of  the  excretions,  which  exist  in 
quantity  so  small  that  their  investigation  seemed  to  belong 
especially  to  the  chemist,  physiologists  having  been  dis- 
couraged, perhaps,  from  studying  them — should  be  thus 
obscure.  But  it  is  surprising  that  an  important  fluid,  the 
bile,  the  product  of  the  largest  gland  in  the  economy  and 
the  one  most  constantly  found  in  the  animal  scale,  should 
be  so  little  understood.  This  has  been  regarded  by  some 
as  a  simple  excrement,  and  by  others  as  not  an  excrementi- 
tious,  but  a  digestive  fluid;  and  so  much  labor  has  been 
expended  by  physiologists  in  endeavors  to  settle  this 
point,  that  no  one  has  pretended  to  give  an  account  of 
its  excrementitious  function,  if  it  has  any,  and  researches 
into  its  digestive  function  have  left  us  almost  entirely  in 
the  dark.  Blondlot  reported  an  observation  on  a  dog 
that  lived  for  five  years  with  a  biliary  fistula  diverting, 
as  it  is  stated,  all  the  bile  from  the  intestines  and  discharg- 
ing it  from  the  body.  The  animal  presented  no  untoward 
symptoms,  died  a  natural  death,  no  bile  found  its  way  into 
the  intestines,  but  it  was  all  discharged.  According  to 
this  observation,  the  bile  would  appear  to  be  purely  an 
excretion.  Schwann,  and  Bidder  and  Schmidt,  in  a  large 
number  of  experiments,  never  succeeded  in  keeping  a  dog 
operated  on  in  this  w^ay  for  more  than  a  few^  weeks;  they 
all  died  with  evidences  of  inanition.  The  bile,  according 
to  these  observations,  is  concerned  chiefly  in  nutrition;  and 
as  it  is  poured  into  the  upper  part  of  the  digestive  tube, 
it  is  important,  probably,  in  digestion.  But  Bidder  and 
Schmidt  do  not  satisfy  us  w^hat  its  digestive  function  is; 
nor  does  Blondlot  say  what  principle  is  excreted  by  it  or 
what  would  be  the  result  of  its  suppression. 

Aside  from  a  few  isolated  facts,  interesting  enough, 
but  indicating  nothing  definite,  this  is  all  w^e  know  of  the 
function  of  the  bile.     But  what  physiologist  does  not  feel 


i66  NEW   FUNCTION  OF  THE    LIVER 

this  hiatus  in  his  science;  or  what  practical  physician  does 
not  feel  and  know  the  importance  of  the  function  of  the 
bile!  It  needs  no  inquiry  into  natural  history,  showing  thq 
universality,  almost,  of  the  liver  in  the  animal  scale,  to  im- 
press upon  the  physician  at  the  bedside  the  importance  of 
the  bile.  A  patient  is  suffering  from  an  obscure  ailment, 
which  he  may  call  biliousness  or  derangement  of  the  liver, 
and  which,  in  some  unexplained  way,  is  relieved  by  a  mer- 
curial purge.  The  practitioner  knows  that  the  bile-secret- 
ing function  of  the  liver  is  important,  but  does  not  learn  it 
from  the  physiologist.  Every  practitioner  must  feel  that 
the  liver  has  a  function  which  must  be  explained  him  by 
the  physiologist,  before  he  can  avoid  treating  a  large  class 
of  diseases  empirically. 

The  bile  has  an  important  excretory  function,  which  is 
liable  to  many  disorders;  and  this  function  I  hope  to  be 
able,  in  the  present  article,  to  describe. 

It  is  evident  from  the  preceding  remarks  that  the  physi- 
ological history  of  the  bile  remains  to.  be  written.  The 
subject  is  too  interesting  and  important  not  to  engage  the 
mind  of  the  experimental  physiologist.  It  is  difficult  at 
first  sight  to  harmonize  statements,  to  which  reference 
has  just  been  made,  of  experimenters,  equally  entitled  to 
consideration,  which  are  diametrically  opposite.  But  of 
course  the  philosophical  method  of  studying  the  bile  is  first 
to  settle  w^iether  it  is  excrementitious  or  recrementitious. 
If  the  former,  what  substance  is  excreted,  and  where  is  it 
formed?  If  the  latter,  what  function  does  it  perform  in 
any  of  the  processes  of  nutrition.  With  the  view  to  har- 
monize, if  possible,  in  my  own  mind,  the  opposite  state- 
ments of  Bidder  and  Schmidt  and  of  Blondlot,  I  attempted 
some  time  ago  to  establish  biliary  fistulre  in  dogs.  The 
first  experiments  were  made  in  New  Orleans  in  the  winter 
of  1860-61,  but  were  all  of  them  unsuccessful,  no  animal 
surviving  the  operation  more  than  three  days.  The  ex- 
periments were  discontinued  at  that  time  but  were  renewed 
in  the  winter  of  1861-62  at  the  Bellevue  Hospital  Medical 
College.  After  a  number  of  trials  which  were  no  more 
successful  than  those  made  the  previous  winter,  I  succeed- 
ed in  performing  the  operation  with  considerable  rapidity 
and  with  very  little  disturbance  of  the  abdominal  organs, 
and  in  one  animal  the  success  was  complete. 


NEW    FUNCTION   OF   THE    LIVER  167 

Experiment  I. — The  operation  was  performed  by  making  an 
incision  into  the  abdomen  in  the  median  line  just  below  the  ensi- 
form  cartilage,  about  three  inches  in  length.  The  edge  of  the  liver 
was  carefully  raised,  the  bile  duct  isolated,  and  two  ligatures  ap- 
plied, one  next  the  duodenum  and  the  other  near  the  junction  of 
the  ductus  choledochus  with  the  cystic  duct,  the  intermediate  por- 
tion being  excised.  The  fundus  of  the  gall-bladder  was  then  drawn 
to  the  upper  part  of  the  wound,  an  incision  made  in  it  of  about 
an  inch  in  length,  the  bile  evacuated,  and  the  edges  attached  to 
the  skin  by  points  of  interrupted  suture.  The  wound  was  then 
carefully  closed  around  the  opening  into  the  gall-bladder. 

This  is  nearly  the  proceeding  recommended  by  Blondlot,  who 
prefers,  however,  to  operate  while  the  animal  is  fasting,  as  the 
gall-bladder  is  then  distended  and  can  be  easily  found.  I  have 
preferred  to  operate  after  feeding,  when  the  gall-bladder  is  com- 
paratively empty,  as  there  is  no  great  difificulty  in  finding  it,  and 
in  evacuating  its  contents  less  bile  is  likely  to  find  its  way  into  the 
peritoneal  cavity,  which  is  one  of  the  causes  of  the  intense  peri- 
tonitis which  follows  this  operation. 

The  animal  ate  well  the  day  after  the  operation,  the  bile  flowed 
freely  from  the  fistula  and  was  entirely  cut  off  from  the  intestine, 
as  shown  by  post-mortem  examination.  No  symptoms  supervened 
except  those  produced  by  the  diversion  of  the  bile  from  its  normal 
course.  This  operation  was  performed  on  the  15th  of  November, 
1861,  and  the  animal  lived  thirty-eight  days. 

In  no  observation  that  I  have  found  recorded  has  the  animal 
been  so  free  from  inflammation  consequent  upon  so  serious  an 
operation ;  and  this  seemed  a  most  favorable  opportunity  for  de- 
termining whether  an  animal  could  live  with  the  bile  shut  off  from 
the  intestinal  tube  and  discharged  by  a  fistula.  In  this  case  the 
animal  gradually  lost  flesh  and  strength,  his  appetite  becoming 
voracious,  until  finally  he  died  of  inanition ;  the  observation  agree- 
ing in  every  important  particular  with  the  experiments  of  Schwann, 
and  of  Bidder  and  Schmidt. 

Experiment  II. — This  experiment  was  undertaken  to  ascer- 
tain, if  possible,  the  entire  quantity  of  bile  secreted  in  twenty- 
four  hours.  A  fistula  was  made  into  the  ductus  communis  chole- 
dochus, the  duct  being  divided  and  a  silver  tube  introduced.  The 
experiment  did  not  succeed  in  the  point  of  view  in  which  it  was 
undertaken,  and  about  forty-eight  hours  after  the  operation,  the 
tube  dropped  out.  After  the  removal  of  the  tube  the  bile  ceased 
to  flow  externally,  and  the  animal  did  not  appear  to  suffer  any  bad 
effects  from  the  experiment.  Thirty  days  after  the  operation,  the 
animal  having  entirely  recovered,  he  was  killed  by  section  of  the 
medulla  oblongata,  and  the  parts  carefully  examined.  The  post- 
mortem examination  I  transcribe  from  my  note-book. 

"  On  post-mortem  examination  the  liver  was  found  adherent 
to  the  diaphragm  over  the  greater  part  of  its  convex  surface. 
There  were  evidences  of  limited  inflammation  over  the  duodenum. 
The  liver  itself  was  normal.  Upon  opening  the  duodenum,  the 
papillae  which  marks  the  opening  of  the  ductus  communis  chole- 


i68  NEW    FUNCTION  OF  THE    LIVER 

dochus  was  normal  in  appearance.  A  small  silver  stilet  was  in- 
troduced into  the  duct.  For  a  long  time  it  was  impossible  to  find 
any  communication  between  the  upper  part  of  the  duct  and  the 
intestine;  but  at  last,  after  patient  searching  (knowing  that  no  bile 
was  discharged  from  the  body  and  that  it  was  absolutely  certain 
that  a  communication  existed  with  the  duodenum),  a  communica- 
tion was  found.  In  Blondlot's  case  there  probably  was  a  commu- 
nication reestablished  which  escaped  his  observation." 

In  the  remarkable  observation  reported  l)y  Blondlot,. 
in  which  the  animal  survived  for  so  long  a  period,  the  suc- 
cess is  attributed  to  the  fact  that  the  dog  was  prevented 
from  licking  the  bile  as  it  flowed  from  the  fistula,  Blondlot 
stating  that  so  soon  as  the  animal  was  prevented  from  lick- 
ing the  bile,  nutrition  began  to  improve.  Anxious  tO' 
carry  out  all  the  precautions  which  had  been  adopted,  I 
so  muzzled  the  animal  in  Experiment  I.,  covering  the  lower 
part  of  the  muzzle  with  oiled  silk,  that  it  was  impossible 
for  him  to  swallow  a  drop  of  the  bile.  This  muzzle  was 
kept  on  till  the  death  of  the  animal,  but  the  proceeding 
had  no  effect  on  his  nutrition.  The  bile  flowed  so  freely 
from  the  fistula  that  all  the  lower  part  of  the  animal  was 
covered  with  it.  It  was  not,  however,  until  I  made  the 
post-mortem  examination  in  the  second  experiment  that 
I  was  able  to  see  the  difficulty  which  I  had  experienced 
in  harmonizing  the  observations  of  the  different  experi- 
menters I  have  quoted.  In  the  lower  animals — in  dogs, 
at  least — ducts  have  a  remarkable  tendency  to  reestablish 
themselves.  Any  one  who  has  operated  much  upon  the 
glands  can  hardly  fail  to  have  noticed  this  fact.  The  pan- 
creatic duct,  for  example,  after  having  been  divided  and 
a  tube  introduced,  invariably  becomes  reestablished  after 
the  simple  removal  or  dropping  out  of  the  tube.  It  was 
so  in  Experiment  II.,  in  which  the  tube  dropped  out  of 
the  bile  duct.  The  duct  undoubtedly  became  reestab- 
lished, for  no  bile  flowed  externally  for  nearly  a  month,  the 
animal  enjoying  perfect  health,  and  the  fluid  necessarily 
being  emptied  into  the  intestine;  yet  it  was  with  the  great- 
est difficulty  that  the  communication  could  be  found  with 
the  probe,  and  it  was  only  after  long  searching,  knowing 
that  there  must  be  a  communication,  that  it  was  discovered 
at  all.  Taking  into  consideration  the  great  difficulty  I  had 
in  finding  the  passage  in  this  instance,  and  after  having 
carefully  examined  the  case  reported  by  Blondlot,  I  have 


NEW    FUNCTION    OF  THE    LIVER  169 

concluded  that  a  communication  existed  in  his  experiment 
which  escaped  observation,  but  by  means  of  which  a  large 
quantity  of  bile  found  its  way  into  the  intestine/'^ 

In  regard  to  the  digestive  function  of  the  bile,  it  is 
sufficient  to  state  here  that  the  experiments  which  I  have 
made  on  this  subject  have  led  me  to  believe  that  this  fluid 
has  an  important  ofifice  in  connection  with  the  function 
of  digestion — one,  indeed,  which  is  essential  to  life.  The 
nature  of  its  of^ce,  however,  is  not  understood  and  can 
be  settled  only  by  a  long  and  carefully  executed  series  of 
experimental  researches  which  would  probably  involve  the 
whole  subject  of  digestion.  This  I  hope  to  be  able  to  pre- 
sent in  another  paper.  There  is,  however,  another  function 
of  the  bile  entirely  distinct  from  the  preceding.  It  is  the 
separation  from  the  blood  of  cholesterin,  an  excremen- 
titious  substance,  which  is  formed  by  the  destructive  as- 
similation of  certain  tissues  of  the  body.  Though  not  dis- 
charged from  the  body  as  cholesterin,  it  being  first  changed 
into  another  substance,  it  is  separated  in  that  form  from 
the  blood  and  poured  into  the  intestine  by  the  ductus  com- 
munis choledochus.  This  new  excretory  function  of  the 
bile  will  form  a  great  part  of  the  subject  of  this  paper;  the 
recrementitious  function,  which  is  necessary  to  complete 
the  physiological  history  of  this  fluid,  being  deferred. 

It  will  be  found  that  cholesterin  is  the  most  important 
excretion  separated  by  the  liver,  as  urea  is  the  most  im- 
portant excretion  separated  by  the  kidneys;  and  the  study 
of  this  substance  will  necessarily  involve  the  depurative 
function  of  the  liver.  I  shall  therefore  begin  with  choles- 
terin, and  endeavor  to  show  where  it  is  formed  in  the 
economy,  by  following  the  blood  in  its  passage  through 
various  organs.  This  will  necessarily  involve  a  description 
of  the  chemical  processes  which  have  been  employed  in 
its  extraction.     I  shall  then  endeavor  to  show  where  the 

*  An  account  of  this  experiment  is  to  be  found  in  an  article  entitled  "  Essai 
sur  les  fonctions  du  foi  et  de  ses  annexes,"  par  N.  Blondlot,  1846.  The  post- 
mortem examination  of  the  animal,  made  more  than  five  years  after  the  estab- 
lishment of  the  fistula,  was  published  in  a  little  memoir  complementary  to  the 
preceding,  entitled  "  Inutilite  de  la  bile  dans  la  digestion,"  1851.  It  is  not 
contemplated  to  enter  into  a  full  discussion  of  the  views  of  Blondlot  and  others 
on  the  uses  of  the  bile  in  digestion.  That  subject  will  be  taken  up  in  another 
paper  in  which  mainly  the  digestive  properties  of  the  bile  will  be  considered. 
In  this  connection  it  is  proposed  to  take  up  only  the  excrementitious  function 
of  the  bile. 


I70  NEW    FUNCTION   OF  THE    LIVER 

cholesterin  is  removed  from  the  blood,  by  the  same  method 
of  investigation.  The  next  step  will  be  to  follow  it  out 
of  the  body  and  study  the  change  which  it  undergoes  in 
its  passage  through  the  alimentary  canal.  Having  de- 
scribed the  process  of  formation  in  the  tissues,  separation 
from  the  blood  by  the  liver  and  final  discharge  from  the 
body,  1  shall  endeavor  to  show,  finally,  the  effects  of  in- 
terruption of  this  function  of  the  liver  upon  the  economy. 
This  will  lead  into  j^athology,  and  a  host  of  diseases  will 
arise  which  may  be  dependent  on  a  disturbance  of  the  ex- 
cretory function  of  the  liver.  I  shall  be  enabled  to  draw 
the  line  more  closely  between  conditions  in  which  there 
is  resorption  simply  of  the  innocuous  coloring  matter  of 
the  bile,  and  those  diseases  in  which  there  is  a  failure  to 
separate  the  excretions  from  the  blood.  These  conditions, 
it  is  well  known,  are  widely  different  as  to  gravity,  and 
the  distinction  between  them  is  of  great  importance.  The 
latter  condition,  characterized  by  the  retention  of  choles- 
terin  in  the  blood,  will  be  treated  of  under  the  name  of 
■cholesteremia. 

CHOLESTERIN 

Chemical  Characters. — Cholesterin  is  a  non-nitro- 
genous substance,  having  all  the  properties  of  the  fats, 
excepting  that  of  saponification  with  the  alkalies.  Its 
chemical  formula  is  usually  given  as  C25H22O.  It  belongs 
to  a  class  of  fatty  substances  which  are  non-saponifiable, 
which  have  been  grouped  by  Lehmann  under  the  name 
of  lipoids.  This  class  is  composed  of  cholesterin  and  sero- 
lin,  which  are  animal  substances;  castorin,  from  the  cas- 
toreum,  and  ambrein,  from  amber.  To  this  he  adds  a  sub- 
stance discovered  in  a  uterine  tumor  by  Busch,  called 
inosterin.  Cholesterin  is  neutral,  inodorous,  crystalliza- 
ble,  insoluble  in  water,  soluble  in  ether,  very  soluble  in  hot 
alcohol,  though  sparingly  soluble  in  cold.  It  burns  with  a 
bright  flame,  but  is  not  attacked  by  the  alkalies,  even  after 
prolonged  boiling.  When  treated  with  strong  sulphuric 
acid,  it  strikes  a  peculiar  red  color,  which  is  mentioned  by 
•some  as  characteristic  of  cholesterin.  I  have  found  that  it 
possesses  this  character  in  common  with  serolin.* 

*  This   reaction    of  serolin    is   mentioned   by   Berard,   in   his  "  Cours  de 
physiologic,"  tome  iii.,  p.  117. 


NEW    FUNCTION   OF  THE    LIVER  171 

Forms  of  its  Crystals. — Cholesterin  may  easily  and 
certainly  be  recognized  by  the  form  of  its  crystals,  the 
characters  of  which  can  be  made  out  by  means  of  the  mi- 
croscope. They  are  rectangular  or  rhomboidal,  exceeding- 
ly thin  and  transparent,  of  variable  size,  with  distinct  and 
generally  regular  borders,  and  frequently  arranged  in  layers 
with  the  borders  of  the  lower  crystals  showing  through 
those  which  are  superimposed.  This  arrangement  of  the 
crystals  takes  place  when  cholesterin  is  present  in  con- 
siderable quantity.  In  pathological  specimens  they  gen- 
erally are  few  in  number  and  isolated.  The  plates  of  cho- 
lesterin are  frequently  marked  by  a  cleavage  at  one  corner, 
the  lines  running  parallel  to  the  borders;  frequently  they 
are  broken,  and  the  line  of  fracture  is  generally  undulat- 
ing. Lehmann  attaches  a  great  deal  of  importance  to 
measurements  of  the  angles  of  the  rhomboid.  According 
to  this  author,  the  obtuse  angles  are  100°  30',  and  the 
acute  79°  30'.  I  have  lately  examined  a  great  number  of 
specimens  of  cholesterin,  extracted  from  the  blood,  bile, 
brain,  liver,  and  occurring  in  tumors,  and  am  confident 
that  the  crystals  have  no  definite  angle.  Frequently  the 
plates  are  rectangular,  and  sometimes  almost  lozenge- 
shaped.  It  is  by  the  transparency  of  the  plates,  the  paral- 
lelism of  their  borders,  and  their  tendency  to  break  in 
parallel  lines  that  we  recognize  them  as  formed  of  choles- 
terin. Lehmann  seems  to  consider  the  tablets  of  this  sub- 
stance as  regular  crystals  having  invariable  angles.  From 
examination  during  crystallization,  I  am  disposed  to  think 
that  they  are  not  crystals  but  fragments  of  micaceous 
sheets,  which,  from  their  extreme  tenuity,  are  easily  broken. 
In  examining  a  specimen  from  the  meconium,  wdiich  I 
extracted  with  hot  alcohol,  I  was  able  to  see  a  transparent 
film  forming  on  the  surface  of  the  alcohol  soon  after  it 
cooled;  this,  on  microscopic  examination,  in  situ,  disturb- 
ing the  fluid  as  little  as  possible,  was  found  to  be  marked 
by  long  and  parallel  lines.  When  the  fluid  had  partially 
evaporated,  it  became  broken  and  took  the  form  of  the 
ordinary  crystals  of  cholesterin,  but  they  were  larger  and 
more  regular.  The  beauty  of  the  tablets  at  this  stage 
could  not  be  adequately  represented.  They  were  exceed- 
ingly thin,  and  regularly  divided  into  delicate  plates,  with 
the    characteristic    corner    cleavages    of    cholesterin;    and 


172  NEW    FUNCTION   OF  THE    LIVER 

as  the  focus  of  the  instrument  was  chanq-ed,  new  layers, 
with  different  arrangement,  were  brought  into  view.  I 
have  attempted  to  give  an  idea  of  the  form  of  these  tal)lets 
in  Fig.  I ;  but  it  is,  of  course,  impossible  to  represent  their 
pale,  but  beautifully  distinct  borders.  As  has  been  re- 
marked by  Rol)in,  the  borders  of  these  crystals  can  be  but 
imperfectly  imitated  by  a  line;  there  is  no  line  in  the  ob- 
ject itself,  but  the  edge  shows  where  the  tablet  ceases. 
(See  Fig.  i.) 

The  crystals  generally  are  colorless,  but  when  present 
in  colored  fluids,  may  take  a  yellowish  tint  or  even  be- 
come very  dark.  They  may  still  be  recognized,  however, 
by  the  characters  of  form  just  described. 

Crystals  of  cholesterin  melt  at  293°  Fahr.,  but  are 
formed  again  when  the  temperature  falls  below  that  point. 
According  to  Lehmann,  they  may  be  distilled  in  vacuo  at 
680°  without  decomposition.  The  determination  of  the 
fusing  point  is  one  of  the  means  of  distinguishing  it  from 
serolin,  which  fuses  at  90.8°. 

Situations  of  Cholesterin. — Most  authors  state 
that  cholesterin  is  found  in  the  bile,  blood,  liver,  brain 
and  nerves,  crystalline  lens,  meconium  and  the  fecal  mat- 
ter. I  have  found  the  cholesterin  in  all  these  situations 
invariably,  excepting  the  feces,  where  it  was  seen  but  once 
after  a  number  of  examinations;  and  in  studying  the  works 
of  those  who  have  investigated  this  substance,  I  can  find 
no  one  who  has  found  it  in  the  normal  feces.  It  is  found 
in  large  quantities  in  the  meconium,  from  which,  perhaps, 
it  is  most  easily  extracted  in  a  state  of  purity,  and  has  been 
extracted  from  the  feces  of  animals  in  a  state  of  hiberna- 
tion; but  though  it  may  occasionally  be  found  in  the  feces 
in  disease  and  in  animals  after  long  fasting,  I  am  confident 
that  it  never  occurs  under  ordinary  conditions.  The  anal- 
ysis of  the  fecal  matter  is  so  unattractive  that  it  has  been 
very  much  neglected  by  chemists;  and  until  a  few  years 
ago,  when  an  elaborate  analysis  was  made  by  Marcet,  to 
which  reference  will  hereafter  be  made,  the  analyses  of 
Berzelius  furnished  nearly  all  our  data  on  this  subject.  Cho- 
lesterin forms  the  greatest  part  of  biliary  calculi,  which  in- 
deed consist  generally  of  nothing  but  cholesterin,  coloring 
matter  and  mucus.  It  is  found  in  a  large  number  of  mor- 
bid deposits.    Few  specimens  of  cancer  are  examined  with- 


NEW   FUNCTION   OF  THE    LIVER 


173 


out  discovering  tablets  of  cholesterin.  It  is  very  abundant 
in  encysted  tumors.  According  to  Robin,  atheromatous 
deposits,  which  are  found  in  the  middle  coats  of  the  arteries, 
are  often  composed  of  cholesterin.  It  sometimes  forms 
distinct  tumors  or  deposits  in  the  substance  of  the  brain. 
I  lately  had  an  opportunity  of  examining  a  tumor  from 
"the  brain,  at  the  Belle vue  Hospital,  which  consisted  of 
nearly  pure  cholesterin.  It  has  often  been  found  in  the 
fluid  of  hydrocele,  in  the  fluid  of  ovarian  cysts,  in  crude 
tubercle,  in  epithelial  tumors  and  in  pus.  The  propor- 
tion in  which  it  exists  in  the  fluids  of  the  body  is  very  small. 
I  have  made  a  number  of  quantitative  analyses  of  the  blood, 
the  results  of  which  I  give  in  the  following  table  with  some 
other  analyses  which  have  been  made  for  this  substance. 
I  also  give  the  quantity  which  I  have  found  in  the  other 
situations  in  which  it  exists.  The  variations  in  dififerent 
parts  of  the  circulation  and  in  diseased  conditions  will  be 
given  in  another  table.  The  quantity  in  the  brain  and 
crystalline  lens  has,  I  believe,  never  before  been  estimated: 

Table  of  Quantity  of  Cholesterin  in  Various  Situations 


Situation. 


Venous  blood  (male) 

"  (female). .  .  .  . 

"  (male  set.  35) 

"  (male  set.  22) 

"  (male  set.  24) 

Bile  (human) 

"    (normal,  of  ox) 

"    (human) 

Meconium 

Brain  (human) , 

■Crystalline  lens  (ox)  * 


Observer. 


Becquerel  and  Rodier. 

Becquerel  and  Rodier. 

Flint. 

Flint. 

Flint. 

Frerichs. 

Berzelius. 

Flint. 

Simon. 

Flint. 

Flint. 

Flint. 

Flint. 


Quantity 
examined. 


312. 0S3 

187.843 
102.680 


224.588 
170.541 

159-753 
150.881 
135.020 


Cholesterin 
per  1,000  pts. 


0.090 
0.090 

0.445 
0.653 

0.751 
I  .60a 
I  .000 
0.618 
160.000 
6.245 
7.729 
11.456 
0.907 


Forms  under  which  Cholesterin  exists  in  the 
Organism. — In  the  fluids  of  the  body  cholesterin  exists 
in  a  state  of  solution,  but  by  virtue  of  what  constituents 
it  is  held  in  solution  is  not  entirely  settled.  It  is  stated 
that  the  biliary  salts  have  the  power  of  holding  it  in  solu- 


*  In  this  examination  four  fresh  crystalline  lenses  of  the  ox  were  used. 


174  NEW    FUNCTION    OF  THE    LIVER 

tion  in  the  bile,  and  that  the  small  quantity  of  fatty  acids 
which  are  contained  in  the  blood  hold  it  in  solution  in  that 
fluid,  but  direct  experiments  on  this  point  are  wanting. 
In  the  nervous  substance  and  in  the  crystalline  lens  it  is 
united,  "  molecule  a  molecule,"  to  the  other  elements  which 
go  to  make  up  these  tissues.  After  it  is  discharged  into 
the  intestinal  canal,  when  it  is  not  changed  into  stercorin, 
it  is  to  l)e  found  in  a  crystalline  form,  as  in  the  meconium 
and  in  the  feces  of  animals  in  a  state  of  hil)ernation.  In 
pathological  fluids  and  in  tumors  it  is  found  in  a  crystal- 
line form  and  may  be  detected  by  microscopic  examination. 

Process  for  the  Extraction  of  Cholesterin. — 
Without  describing  the  processes  which  have  been  em- 
ployed by  other  observers  for  the  extraction  of  cholesterin 
from  the  blood,  bile  and  various  tissues  of  the  body,  I  shall 
confine  myself  to  a  description  of  the  process  which  I  have 
found  most  convenient  to  employ  in  the  analyses  I  have 
made  for  this  substance.  In  analyses  of  gall-stones  the 
process  is  very  simple;  all  that  is  necessary  being  to  pul- 
verize the  mass  and  extract  it  with  boiling  alcohol;  filter 
the  solution  while  hot,  the  cholesterin  being  deposited  on 
cooling.  If  the  crystals  are  colored,  they  may  be  redis- 
solved  and  filtered  through  animal  charcoal.  This  is  the 
proceeding  employed  by  Poulletier  de  la  Salle,  Fourcroy 
and  Chevreul.  It  is  only  when  this  substance  is  mixed 
with  fatty  matters  that  its  isolation  is  a  matter  of  any 
difBculty.  In  extracting  cholesterin  from  the  blood  I  have 
operated  on  both  the  serum  and  clot,  and  in  this  way  have 
been  able  to  demonstrate  it  in  greater  quantities  in  this 
fluid  than  have  been  observed  by  others,  who  have  em- 
ployed only  the  serum.  The  following  is  the  process  for 
quantitative  analysis,  which  I  fixed  upon  after  a  number  of 
experihients. 

The  blood,  bile  or  brain,  as  the  case  may  be,  is  first 
carefully  weighed,  then  evaporated  to  dryness  over  a  water- 
bath,  and  carefully  pulverized  in  an  agate  mortar,  so  as 
to  collect  every  particle.  The  powder  is  then  treated 
with  ether,  in  the  proportion  of  about  a  fluidounce  for 
every  hundred  grains  of  the  original  weight,  for  twelve 
to  twenty-four  hours,  agitating  the  mixture  occasionally. 
The  ether  is  then  separated  by  filtration,  throwing  a 
little  fresh  ether  on  the  filter  so  as  to  wash  through  every 


NEW    FUNCTION   OF  THE    LIVER  175 

trace  of  the  fat,  and  the  sohition  is  set  aside  to  evap- 
orate.* If  the  fluid,  especially  the  blood,  has  been  care- 
fully dried  and  pulverized,  when  the  ether  is  added  it  di- 
vides it  into  a  very  fine  powder  and  penetrates  every  part. 
After  the  ether  has  evaporated,  the  residue  is  extracted 
with  boiling  alcohol  in  the  proportion  of  about  a  fluidrachm 
for  every  hundred  grains  of  the  original  weight  of  the  speci- 
men, filtered,  while  hot,  into  a  watch-glass  and  allowed  to 
evaporate  spontaneously.  To  keep  the  fluid  hot  while 
filtering,  the  whole  apparatus  may  be  placed  in  the  cham- 
ber of  "a  large  water-bath,  or  as  the  filtration  is  generally 
rapid,  the  funnel  may  be  warmed  by  plunging  it  into  hot 
water,  or  steaming  it,  taking  care  that  it  be  carefully  wiped. 
We  now  have  the  cholesterin  mixed  with  a  certain  quantity 
of  saponifiable  fat.  After  the  fluid  has  evaporated,  we  can 
see  the  cholesterin  crystallized  in  the  watch-glass,  mingled 
with  masses  of  fat.  This  we  remove  by  saponification  with 
an  alkali ;  and  for  this  purpose,  we  add  a  moderately  strong 
solution  of  caustic  potash,  which  we  allow  to  remain  in 
contact  w'ith  the  residue  for  one  to  tw^o  hours.  If  much 
fat  is  present,  it  is  best  to  subject  the  mixture  to  a  tem- 
perature a  little  below  the  boiling  point;  but  in  analyses 
of  the  blood  this  is  not  necessary.  The  mixture  is  then 
to  be  largely  diluted  with  distilled  water,  thrown  upon  a 
small  filter,  and  thoroughly  washed  till  the  solution  which 
passes  through  is  neutral.  We  then  dry  the  filter,  and  fill 
it  up  with  ether,  w'hich,  in  passing  through,  dissolves  out 
the  cholesterin.  The  ether  is  then  evaporated,  the  residue 
extracted  with  boiling  alcohol  as  before,  the  alcohol  col- 
lected on  a  watch-glass  previously  weighed,  and  allowed 
to  evaporate.  The  residue  consists  of  pure  cholesterin, 
the  quantity  of  W'hich  may  be  estimated  by  weight. 

The  accuracy  of  this  process  may  be  tested  by  means  of 
the  microscope.  As  the  crystals  have  so  distinctive  a  form 
under  the  microscope,  it  is  easy  to  determine  by  examining 
the  watch-glass  that  it  has  been  obtained  in  a  state  of 
purity.  In  making  this  analysis  quantitatively  it  is  nec- 
essary to  be  very  careful  in  all  the  manipulations;  and  for 
determining  the  weight  of  such  minute  quantities,  an  accu- 

*  The  ether  may  be  preserved  bv  distillation,  instead  of  allowintr  it  to  evapo- 
rate, but  with  the  small  quantity  usually  employed  this  is  hardly  worth  while. 


176  NEW    FUNCTION   OF   THE    LIVER 

rate  and  delicate  balance,  one,  at  least,  that  will  turn  with 
the  thousandth  of  a  gramme,  carefully  adjusted,  must  be 
employed.  With  these  precautions  the  quantity  of  cho- 
lesterin  in  any  fluid  or  solid  may  be  determined  with  per- 
fect accuracy.  The  quantity  of  cholesterin  may  be  esti- 
mated in  fifteen  or  twenty  grains  of  blood.  In  analyzing 
the  brain  and  bile  I  found  it  necessary  to  pass  the 
first  ethereal  solution  through  animal  charcoal  to  get  rid 
of  the  coloring  matter.  In  doing  this  the  charcoal  must 
be  washed  with  fresh  ether  till  the  solution  which  passes 
through  is  brought  up  to  the  original  quantity.  The  other 
manipulations  are  the  same  as  in  examinations  of  the  blood. 
In  examining  the  meconium  I  found  that  the  cholesterin 
which  crystallized  from  the  first  alcoholic  extract  was  so 
pure  that  it  was  not  necessary  to  subject  it  to  the  action 
of  an  alkali. 

I  am  aware  that  in  describing  the  process  for  the  ex- 
traction of  cholesterin  I  have  entered  into  details  which 
would  be  superfluous  for  the  practical  chemist.  But  the 
extraction  of  this  substance  from  the  blood  is  so  simple, 
and  the  results  of  the  examination  of  blood  in  different 
parts  of  the  circulatory  system  have  been  so  striking  and 
important,  that  I  can  not  but  indulge  the  hope  that  the 
observations  which  follow  will  be  verified  by  those  who 
may  not  be  skilful  practical  chemists.  Almost  any  one  is 
competent  to  make  a  quantitative  analysis  of  the  blood 
for  cholesterin.  It  simply  requires  six  days  for  the  process, 
and  a  number  of  analyses  may  be  carried  on  at  the  same 
time.  It  requires  one  day,  after  the  blood  has  been  dried 
and  pulverized,  for  the  ether  to  act  upon  it;  the  next  morn- 
ing it  is  filtered  and  set  aside;  the  next  morning  it  will  be 
dry  and  may  be  extracted  with  alcohol  and  set  aside  to 
evaporate;  the  next  morning  it  may  be  treated  with  pot- 
ash, filtered,  and  the  filter  washed  with  water;  the  following 
day  it  may  be  washed  with  ether  and  set  aside  to  evapo- 
rate; the  following  day  it  will  have  evaporated  and  may 
be  extracted  with  hot  alcohol;  and  the  following  day  the 
alcohol  will  have  evaporated  and  the  specimen  may  be 
examined  by  the  microscope  and  weighed.  All  that  is  re- 
quired is  a  little  care  in  the  performance  of  these  simple 
manipulations — which  one  with  a  slight  acquaintance  with 
operations  in  chemistry  may  perform  at  once,  and  one  or 


NEW    FUNCTION   OF   THE    LIVER  177 

two  trials  will  enable  a  novice  to  execute — and  accuracy 
in  weighing,  which  is,  indeed,  the  most  delicate  part  of 
the  process. 

History  of  Cholesterin. — A  brief  sketch  of  the  his- 
tory of  this  substance  may  not  be  uninteresting.  It  was 
first  obtained  by  PouUetier  de  la  Salle,  in  1782,  who  ex- 
tracted it  from  a  biliary  calculus.  He  communicated  his 
observations  to  Fourcroy,  who  pubHshed  them,  after  hav- 
ing verified  his  experiments,  the  death  of  the  discoverer 
preventing  him  from  making  his  observations  public. 
Afterward,  in  examining  an  old  hardened  liver,  Fourcroy 
found  a  concrete  oily  substance  analogous  to  that  dis- 
covered by  PouUetier.  He  imagined  that  the  liver  had 
become  changed  into  a  substance  resembling  spermaceti. 
Cholesterin  was  afterward  found  in  gall-stones,  by  Vicq 
d'Azyr,  Jaquin,  Titius  and  Kreysig.  In  1791  Fourcroy 
described  a  substance  which  he  called  adipocire,  found 
in  bodies  at  the  Cimetiere  des  Innocents,  which  he  likened 
to  spermaceti  and  to  cholesterin.  He  always,  however, 
made  a  distinction  between  these  substances;  calling  cho- 
lesterin crystallizable  adipocire.  In  18 14  Chevreul  estab- 
lished the  difference  between  adipocire  and  cholesterin, 
giving  a  full  description  of  the  cholesterin.  He  extracted 
it  from  the  bile  of  the  human  subject,  of  the  bear  and  of 
the  pig. 

After  that  time  a  number  of  chemists  found  it  in  gall- 
stones and  in  intestinal  concretions.  Lassaigne  found  it 
in  a  cerebral  tumor,  Guerard  in  hydatid  cysts  of  the  liver, 
Morin  in  the  liquid  from  an  abdominal  tumor,  Caventou 
in  the  matter  from  an  abscess  under  the  malar  bone,  and 
a  number  of  others  in  tumors  in  various  situations.  In 
1830  it  was  discovered  in  the  blood  by  Denis,  and  after- 
ward described  by  Boudet,  who  wrote  an  elaborate  article 
on  the  composition  of  the  serum  of  the  blood  in  1833,  in 
which  he  described  cholesterin  and  a  new  substance 
which  he  called  seroline.*  It  was  also  detected  in  normal 
blood  by  Lecanu  and  Marchand.  Couerbe,  who  made 
elaborate  researches  into  the  chemical  composition  of  the 
cerebral  substance,  pointed  out  the  existence  of  choles- 


*  Boudet,  "  Nouvelles    recherches    sur  la  composition  du   serum  du  sang 
humain." — "  Annales  de  chimie  et  de  physique,"  tom.  lii.,  p.  337. 
12 


178  NEW    FUNCTION    OF  THE    LIVER 

terin  in  the  brain.  Lebert  found  it  in  the  substance  of 
cancerous  tumors,  Curhng  found  it  in  the  fluid  of  hydro- 
cele, Simon  extracted  it  from  the  meconium  and  Preuss 
discovered  it  in  the  substance  of  crude  tubercle.  Of  late 
authors,  Becquerel  and  Rodier  have  been  most  extended 
in  their  investigation  of  this  principle.*  They  have  made 
a  number  of  careful  quantitative  analyses  of  the  blood  for 
this  substance  in  health  and  disease.  Their  observations 
will  be  more  particularly  referred  to  farther  on.f 

Functions  of  Cholesterin. — By  experiments  which 
I  have  performed  upon  the  lower  animals  and  by  certain 
facts  which  have  been  developed  by  observations  on  the 
human  blood  in  health  and  disease,  I  think  I  have  been 
enabled  to  solve  the  problem  of  the  function  of  cholesterin. 

Cholesterin  is  an  excrementitious  product,  formed  in 
great  part  by  the  destructive  assimilation  of  the  brain  and 
nerves,  separated  from  the  blood  by  the  liver,  poured  into 
the  upper  part  of  the  small  intestine  with  the  bile,  trans- 
formed in  its  passage  down  the  alimentary  canal  into  ster- 
corin  (the  seroline  of  Boudet,  a  substance  differing  very 
little  from  cholesterin),  and,  as  stercorin,  discharged  by 
the  rectum. 

The  quotation  with  which  I  prefaced  this  paper  ex- 
presses the  actual  state  of  knowledge  in  regard  to  cho- 
lesterin. Still,  though  our  actual  knowledge  of  its  function 
has  been  so  slight,  a  few  writers  on  chemical  physiology 
and  on  physiology,  taking  the  limited  data  on  this  sub- 
ject, make  reference  to  it  as  an  elTete  substance.  In 
regard  to  its  relation  to  the  brain,  some  think  that  it  is 
formed  in  the  brain  and  taken  up  by  the  blood,  while  others 
think  that  it  is  formed  in  the  blood  and  deposited  in  the 
brain.  All  the  views  in  regard  to  its  efifete  properties  are 
of  course  based  on  the  supposition  that  it  is  discharged 
in  the  feces.  Effete  matters  are  discharged  from  the  body, 
and  this  would  find  its  exit  by  the  anus,  since  it  has  never 

*  "  Traite  de  chimie  pathologique  appliquee  a  la  medecine  pratique,"  par  M. 
Alf.  Becquerel,  Professeur  agrege,  etc.,  et  par  M.  A.  Rodier,  Docteur  en  Mede- 
cine, etc.,  Paris,  1854,  and  "  Recherches  sur  la  composition  du  sang,"  Paris, 
1844. 

f  The  history  of  cholesterin  was  compiled  mainly  from  Robin  and  Verdeil, 
the  "Chimie  anatomique." 


NEW    FUNXTIOX   OF   THE    LIVER  179 

been  detected  in  the  urine.  These  conjectures  have  at- 
tracted little  attention  in  the  scientific  world;  and  these 
views  being  based  on  the  supposition  that  this  substance 
is  found  in  the  fecal  matters,  fall  to  the  ground  from  the 
fact  that  no  one  as  yet  detected  it  in  the  feces.  The  fact 
that  cholesterin  is  so  generally  considered  an  ingredient 
of  the  feces  may  be  thus  explained.  It  is  poured  into  the 
alimentary  canal  with  the  bile:  no  one  has  shown  what 
becomes  of  it,  the  chemistry  of  the  feces  being  little  under- 
stood; and  therefore  it  has  been  assumed  that  it  is  found 
in  the  feces.  That  the  facts  which  we  have  with  regard 
to  cholesterin  render  its  effete  properties  possible,  and 
perhaps  probable,  is  certainly  true;  but  these  facts  are 
merely  sufficient  to  enable  the  scientific  investigator  to 
address  an  intelligent  inquiry  to  Nature  on  this  subject; 
they  do  not  solve  the  question.  In  the  experiments 
which  form  the  basis  of  this  article,  the  inquiry  was  made 
and  the  answer  obtained;  some  others  have,  without  much 
reflection  apparently,  made  simple  statements  which  ap- 
proximate in  some  degree  to  the  facts.  The  only  way  these 
assertions  could  be  sustained  is  by  the  labor  which  I  have 
expended  in  eliciting  from  Nature  a  reply  to  my  interroga- 
tories. 

The  works  which  I  have  had  an  opportunity  of  con- 
sulting where  any  decided  opinion  relative  to  the  function 
of  cholesterin  has  been  expressed,  are  those  of  Carpenter, 
Lehmann.  ]\Iialhe  and  Dalton.* 

Carpenter,  in  the  fifth  American  edition  of  his  "  Human 
Physiology,"  1853,  has  the  following  in  regard  to  the  func- 
tion of  cholesterin: 

"  It  is  also  stated  to  be  a  constituent  of  the  nervous  tissue, 
having  been  extracted  from  the  brain  bv  Couerbe.  and  other  ex- 
perimenters ;  but  it  may  be  doubted  whether  this  is  not  rather  a 
product  of  the  disintegration  of  nerve-substance,  which  is  destined 
to  be  taken  back  into  the  blood  for  elimination  by  the  excretory 
apparatus,  like  the  kreatine  which  may  be  extracted  from  the  juice 
of  flesh,  or  the  urea  which  is  obtainable  from  the  vitreous  humor 
of  the  eye,  both  being  undoubtedly  excrementitious  matters.  For 
cholesterin  is  a  characteristic  component  of  the  biliary  excretion, 
and  is  closely  related  to  its  peculiar  acids:  so'that  it  can  scarcely 
be  looked  upon  in  anv  other  light  than  as  an  excrementitious  prod- 

*  These  authors  are  quoted  in  the  order  in  which  their  publications  ap- 
peared. 


i8o  NEW   FUNCTION   OF  THE   LIVER 

uct,  the  highest  function  of  which  is  to  assist  in  the  support  of 
the  calorifying  process.  It  is  frequently  separated  from  the  blood 
as  a  morbid  product ;  thus  it  is  often  present  in  considerable  quan- 
tity in  dropsical  fluids,  and  particularly  in  the  contents  of  cysts; 
and  it  may  be  deposited  in  the  solid  form  in  degenerated  structures, 
tubercular  concretions,  etc."  * 

In  Lehmann,  I  find  the  following  on  this  subject: 

"  Judging  from  the  mode  of  its  occurrence,  we  must  regard  it 
as  a  product  of  decomposition ;  but  from  what  substances  and  by 
what  processes  it  is  formed,  it  is  impossible  even  to  guess.  Not- 
withstanding the  similarity  which  many  of  its  physical  properties 
present  to  those  of  the  fats,  we  can  hardly  suppose  that  it  takes 
its  origin  from  them,  since  the  fats,  for  the  most  part,  become 
oxidized  in  the  animal  body,  whereas  in  order  to  form  cholesterin, 
they  must  undergo  a  process  of  deoxidation."  f 

I  translate  the  following-  from  Mialhe,  on  "  Chemistry 
applied  to  Physiology  and  Therapeutics,"  Paris,  1856,  the 
paragraph  entitled  "  Source  of  Cholesterine  in  the  Animal 
Economy." 

"  We  have  just  examined  in  what  manner  the  fatty  bodies  pene- 
trate into  the  blood.  Some  eminent  savans  have  held  that  the 
fatty  matters  from  the  exterior  are  the  only  ones  which  exist  in 
the  economy,  and  that  it  is  incapable  of  producing  these  in  itself. 
Now  it  is  an  opposite  opinion  which  tends  to  predominate,  and  the 
majority  of  physiologists  think  that  certain  fatty  bodies  take  origin 
in  the  very  substance  of  our  organism.  This  last  mode  of  origin 
seems  at  least  incontestable  for  the  cholesterine,  which  has  not  yet 
been  found  in  the  vegetable  kingdom. 

"  But  what  are  the  chemico-physiological  reactions  which  pre- 
side over  the  development  of  this  particular  fatty  substance? 

"  There  are  for  us  two  modes  for  comprehending  the  formation 
of  the  cholesterine  at  the  expense  of  the  elements  of  the  blood. 
Cholesterine  may  come  from  the  fatty  matters ;  it  would  be.  in  this 
case,  like  the  final  result  or  last  stage  of  chemical  modifications 
which  the  fatty  matters  undergo  in  the  animal  economy. 

"This  manner  of  viewing  it  is  slightly  probable;  for,  in  order 
that  it  should  be  true,  it  would  be  necessary  that  the  fatty  bodies, 
in  oxidizing,  should  give  rise  to  a  compound  richer  than  they  in 
carbon.  We  know,  indeed,  that  cholesterine  is,  of  all  fatty  bodies, 
the  one  which  contains  the  most  carbon. 

"  We  think  that  we  should  reject  that  opinion  and  stop  at  the 
following: 

"  The  production  of  cholesterine  may  be  attributed  to  a  trans- 
formation of  the  albuminoid  materials,  a  transformation  analogous 

*  Carpenter,  "  Principles  of  Human  Physiology,"  Philadelphia,  1853,  p.  74, 
+  "  Physiological  Chemistry,"  by  Professor  C.  G.  Lehmann,  Philadelphia, 
1855,  vol.  i.,  p.  24S. 


NEW    FUNCTION   OF   THE    LIVER  i8i 

to  that  which  has  been  pointed  out  by  M.  Blondeau  de  Carrolles 
in  cheese,  and  which  that  chemist  has  designated  under  the  name 
of  adipose  fermentation.  The  large  proportion  of  carbon  which 
the  cholesterine  contains,  and  which  approximates  it  to  albuminous 
matters,  would  come  to  the  support  of  that  point  of  view.  The  re- 
tardation of  the  circulation,  and  the  deficiency  of  oxidation  which  is 
the  consequence  of  it,  explains  also  why  the  cholesterine  is  in  much 
greater  proportion  in  the  closed  cavities  than  in  the  blood  itself. 

"  Whichever  it  may  be  of  these  two  opinions,  it  is  incontestable 
for  us  that,  if  the  cholesterine  is  not  burned  with  the  other  matters 
proper  to  respiratory  alimentation,  it  is  solely  on  account  of  its 
chemical  inertia;  cholesterine,  indeed,  is  to  fatty  matters  what 
mannite  is  to  saccharine  substances — what  urea  is  to  albuminoid 
matters;  that  is  to  say,  that  it  constitutes  a  kind  of  caput  mortuum, 
of  which  the  organism  has  only  to  free  itself.  It  is  certain  also, 
for  us,  that  if  the  cholesterine  is  not  found  in  all  the  excrementi- 
tious  liquids,  where  most  of  the  other  products  existing  in  the 
blood  are  found,  it  is  solely  on  account  of  its  insolubility. 

"  The  preceding  remarks  explain  perfectly,  to  our  eyes  at  least, 
why  the  presence  of  cholesterine  has  never  been  established  in  the 
urine  of  man,  either  in  the  form  of  crystals,  or  *  calculi,'  while  this 
substance  is  found  in  the  bile,  where  it  very  often  forms  calculi 
of  considerable  size.  Cholesterine,  indeed,  is  insoluble  in  acid 
liquids,  such  as  the  urine ;  while  it  is  soluble  in  soapy  liquids,  such 
as  the  bile.  Such  is  solely  the  reason  why  the  cholesterine  is  ex- 
creted by  the  biliary  passages."  * 

Finally,  in  Dalton's  "  Treatise  on  Human  Physiology," 
I  find  the  following  paragraph  in  which  the  subject  of 
cholesterin  is  considered: 

"Cholesterine  (C^^H.^O). — This  is  a  crystallizable  substance 
which  resembles  the  fats  in  many  respects,  since  it  is  destitute  of 
nitrogen,  readily  inflammable,  soluble  in  alcohol  and  ether,  and  en- 
tirely insoluble  in  water.  It  is  not  saponifiable,  however,  by  con- 
tact with  the  alkalies,  and  is  distinguished  on  this  account  from 
the  ordinary  fatty  substances.  Tt  occurs,  in  a  crystalline  form, 
mixed  with  coloring  matter,  as  an  abundant  ingredient  in  most 
biliary  calculi,  and  is  found  also  in  different  regions  of  the  body, 
forming  a  part  of  various  morbid  deposits.  We  have  met  with  it 
in  the  fluid  of  hydrocele,  and  in  the  interior  of  many  encysted 
tumors.  The  crystals  of  cholesterine  have  the  form  of  very  thin, 
colorless,  transparent,  rhomboidal  plates,  portions  of  which  are 
often  cut  out  by  lines  of  cleavage  parallel  to  the  sides  of  the  crys- 
tal. They  frequently  occur  deposited  in  layers,  in  which  the  out- 
lines of  the  subjacent  crystals  show  very  distinctly  through  the 
substance  of  those  which  are  placed  above.  Cholesterine  is  not 
formed  in  the  liver,  but  originates  in  the  substance  of  the  brain 

*"Chimie  appliqu^e  a  la  physiologic  et  a  la  therapeutique,"  par  M.   le 
Docteur  Mialhe,  p.  igi.     Paris,  1856. 


i82  NEW    FUNCTION   OF   THE    LIVER 

and  nervous  tissue,  from  which  it  may  be  extracted  in  large  quan- 
tity by  the  action  of  alcohol.  From  these  tissues  it  is  absorbed  by 
the  blood,  then  conveyed  to  the  liver,  and  discharged  with  the 
bile."  * 

The  above  extracts  embrace  all  that  I  have  been  able 
to  find  bearing  on  the  question  of  the  function  of  choles- 
terin.  The  extracts  from  Mialhe  and  Dalton  contain  all 
that  is  said  by  them  on  this  subject.  Those  from  Carpen- 
ter and  Lehmann  contain  only  what  bears  on  the  function 
of  this  substance,  the  chemical  details  being  omitted.  Of 
the  authors  cited,  Mialhe  is  the  most  extended  on  the  sub- 
ject and  is  almost  the  only  one  who  adduces  any  argu- 
ments to  support  his  views;  but  his  opinions  are  biased 
by  the  purely  chemical  view  which  he  takes  of  the  subject, 
and  are  involved  with  the  ideas  with  reference  to  plastic 
and  calorific  food,  now  rejected  by  many  eminent  physiolo- 
gists, and  which,  I  conceive,  will  be  so  little  supported  by 
future  advances  in  science,  that  they  wall  soon  be  universal- 
ly discarded,  in  the  exclusive  sense  in  which  they  are  re- 
ceived by  him.  Putting  these  hypotheses  aside,  examin- 
ing the  actual  state  of  knowledge  in  regard  to  cholesterin, 
it  is  seen  that  its  function,  up  to  this  time,  has  not  been 
established.  I  shall  now  proceed  to  the  facts  which  tend 
to  support  the  statement  I  have  made  on  this  point. 

Cholesterin  exists  in  the  blood,  from  which  it  may  be 
■extracted  in  a  state  of  purity  and  estimated  by  the  pro- 
cess which  I  have  already  indicated.  Becqtierel  and  Ro- 
■dier  have  made  analyses  of  the  healthy  human  blood  for 
this  substance  wdth  the  follow-ing  results: 

Venous  blood  of  the  male 0.09  pt.  per  i.ooo 

"  "         "        female 0.09  "      "        " 

I  have  made  a  quantitative  analysis  of  three  specimens 
of  healthy  human  blood  with  the  following  results: 

Quantity  of  blood.    Cholesterin.  Proportion 
grains.  grains.     peri,ooopts. 

Venous  blood  from  the  arm  ;  male  £et.  35     312.083  0.139         0-445 

"  "  "  (colored)  St.  22     187.843  0.123         0658 

"  "  "  ast.  24     102.680  0.077         0.751 

*  "  A  Treatise  on  Human  Physiology,"  designed  for  the  use  of  Students 
and  Practitioners  of  Medicine.  By  John  C.  Dalton,  Jr.,  M.  D.,  Professor  of 
Physiology  and  Microscopic  Anatomy  in  the  College  of  Physicians  and  Sur- 
geons, New  York,  etc.     Philadelphia,  1861,  p.  189. 


NEW    FUNCTION   OF  THE    LIVER  183 

These  three  analyses  were  all  carried  on  at  the  same 
time,  each  specimen  being  subjected  to  precisely  the  same 
process.  The  results  show  a  wide  range  within  the  limits 
of  health.  The  difference  was  not  due  to  any  variation 
relating  to  the  digestive  process,  as  the  specimens  were  all 
drawn  at  the  same  time,  and  were  taken  from  prisoners 
on  Blackwell's  Island,  who  were  subjected  to  the  same  diet 
.and  ate  at  the  same  time.  It  will  be  seen  by  this  table 
that  I  have  obtained  five  to  eight  times  more  than  is 
indicated  by  Becquerel  and  Rodier.  I  can  explain  this 
only  by  the  fact  that  I  operated  on  the  whole  blood,  while 
they  analyzed  only  the  serum.  Boudet  states  that  it  is 
necessary  to  make  three  to  four  copious  bleedings  and 
mix  the  serum  in  order  to  obtain  a  sufficient  quantity  for 
a  satisfactory  analysis.  I  have  operated  on  about  fifty 
grains  of  blood  with  success  and  have  no  doubt  but  that 
I  should  be  able  to  extract  the  cholesterin  in  a  crystalline 
form  and  estimate  its  quantity  in  fifteen  or  twenty  grains. 
The  purity  of  the  extract  can  easily  be  demonstrated 
by  a  microscopic  examination.  I  conclude,  then,  that 
3.  much  larger  quantity  of  cholesterin  exists  normally  in 
the  blood  than  has  been  supposed,  and  that  its  varia- 
tions in  different  persons,  within  the  limits  of  health,  are 
•considerable. 

The  next  question  which  naturally  arises  is  the  origin 
of  cholesterin.  In  examining  the  situations  in  which  it  is 
found  it  is  seen  that  it  exists  in  largest  quantity  in  the  sub- 
stance of  the  brain  and  nerves.  It  is  also  found  in  the  sub- 
stance of  the  liver,  probably  in  the  bile  which  is  contained 
in  this  organ,  and  in  the  crystalline  lens,  but  with  these 
•exceptions  it  exists  only  in  the  nervous  system  and  blood. 
Two  views  present  themselves  in  regard  to  its  origin. 
Cholesterin  is  deposited  in  the  nervous  matter  from  the 
blood  or  is  formed  in  the  brain  and  taken  up  by  the  blood. 
This  is  a  question,  however,  which  can  be  settled  experi- 
mentally, by  analyzing  the  blood  for  cholesterin  as  it  goes 
to  the  brain  by  the  carotid  and  as  it  comes  from  the  brain 
by  the  internal  jugular.  Cholesterin  being  found  also  in 
the  nerves,  and,  of  course,  a  large  quantity  of  nervous  mat- 
ter existing  in  the  extremities,  it  is  desirable  at  the  same 
time  to  make  an  analysis  of  the  venous  blood  from  the 
general  system. 


i84  NEW   FUNCTION    OF  THE   LIVER 

With  reference  to  this  question  the  following  experi- 
ment was  made: 

Experiment  III. — A  medium-sized  dog,  about  six  months  old, 
fasting,  was  put  under  the  intiucnce  of  ether.  The  carotid  and 
internal  jugular  were  exposed  on  the  left  side  and  the  animal  al- 
lowed to  come  out  from  the  effects  of  the  anesthetic.  Two  hours 
after,  he  was  again  etherized  and  blood  was  taken  from  the  follow- 
ing vessels  in  the  order  in  which  they  are  named:  i,  internal  jugu- 
lar; 2,  carotid;  3,  vena  cava;  4,  hepatic  veins;  5,  hepatic  artery; 
6,  portal  vein.  In  the  operation  of  drawing  the  blood  from  the 
abdominal  vessels,  immediately  after  opening  the  abdomen  a  liga- 
ture was  applied  to  the  vena  cava  and  a  little  blood  taken,  which 
prevented  the  blood  from  the  inferior  extremities  from  mixing  with 
the  hepatic  blood.  The  blood  was  then  taken  from  the  hepatic 
veins,  a  matter  of  some  difificulty,  as  it  is  always  more  or  less 
mingled  with  blood  returning  through  the  thoracic  vena  cava,  and 
a  ligature  was  applied  to  the  hepatic  artery  and  portal  vein.  The 
blood  was  then  drawn  from  the  hepatic  artery  and  portal  vein.*  A 
quantity  of  bile  was  then  taken  from  the  gall-bladder,  and  a  piece 
taken  from  the  substance  of  the  brain.  These  specimens  were 
received  into  carefully  weighed  vessels  and  weighed ;  but  as  I  failed 
to  make  a  quantitative  analysis,  my  process  of  extraction  not  having 
been  perfected,  it  is  unnecessary  to  enter  into  their  details.  They 
were  then  dried  and  pulverized,  treated  with  ether,  evaporated, 
the  residue  extracted  with  hot  alcohol,  allowed  to  evaporate  spon- 
taneously, and  examined  with  magnifying  powers  of  70,  270,  and 
400  diameters  successively.  The  residue  of  the  bile  and  brain  were 
found  to  consist  of  nearly  pure  cholesterin;  but  in  all  the  other 
specimens,  except  that  from  the  internal  jugular,  the  appearance 
of  cholesterin  was  doubtful.  They  all  contained,  with  masses 
of  ordinary  fat,  crystals  of  stercorin.f     There  were  a  few  distinct 

*  The  operation  of  collecting  the  blood  from  any  particular  vessel  is  by  no 
means  so  easy  as  might  at  first  be  supposed.  The  greatest  care  is  necessary  in 
order  to  obtain  it  unmixed.  This  is  particularly  so  in  the  case  of  the  hepatic 
vein,  the  unmixed  blood  from  which  is  exceedingly  difficult  to  obtain.  In  draw- 
ing blood,  the  operation  must  be  done  as  rapidly  as  possible  to  avoid  the  de- 
rangements of  the  circulation  which  arise  from  exposure  of  the  vessels,  pressure, 
etc.  In  taking  blood  going  to  and  coming  from  a  part,  it  must  always  be  taken 
from  the  vein  first ;  as  ligating  or  compressing  the  artery  would  of  course  arrest 
the  circulation.  As  the  blood  in  the  arterial  system  is  not  subject  to  the  same 
changes  in  composition  as  the  blood  in  the  different  veins,  any  specimen  of 
arterial  blood  will  represent  the  blood  going  to  a  part,  unless,  like  the  liver,  it 
receives  blood  from  the  venous  system.  The  collection  of  blood  I  have  found 
the  most  difficult  part  of  these  investigations. 

f  Stercorin,  or  serolin,  is  a  non-saponifiable  fatty  substance  resembling 
cholesterin  in  many  of  its  chemical  properties,  but  fusing  at  a  much  lower  tem- 
perature. It  was  discovered  in  the  serum  of  the  blood  by  Boudet  about  1833. 
It  crystallizes  in  the  form  of  needles,  which  will  be  more  particularly  described 
when  I  treat  of  the  extraction  of  this  substance  from  the  feces.  As  I  have 
found  it  in  great  abundance  in  the  feces  and  am  disposed  to  doubt  its  existence 
as  a  natural  constituent  of  the  serum  of  the  blood,  I  have  called  it  stercorin,. 
for  reasons  which  will  be  more  fully  exposed  farther  on. 


NEW    FUNCTION   OF   THE    LIVER  185 

plates  of  cholesterin  in  the  specimen  from  the  internal  jugular. 
The  specimens  were  then  treated  with  a  solution  of  caustic  potash 
and  set  aside.  In  two  days  part  of  the  potash  was  removed  with 
bibulous  paper  and  portions  of  the  precipitates  taken  out,  placed 
upon  slides,  and  examined  microscopically  with  ^th  and  -xVth  inch 
objectives  successively.  The  watch-glasses  were  then  set  aside, 
carefully  protected  from  dust,  and  examined  again  ten  days  after, 
when  they  had  become  entirely  dry.  The  following  was  the  re- 
sult of  the  examinations  of  the  extracts  of  blood  from  the  carot- 
id, internal  jugular,  vena  cava  and  the  extract  of. the  brain.  The 
examination  of  the  other  specimens  has  nothing  to  do  with  the 
question  now  under  consideration,  and  their  description  is  de- 
ferred. 

Blood  from  the  Carotid  Artery. — First  examination,  three 
days  after  the  operation,  discovered  a  large  number  of  small  crys- 
tals of  stercorin  and  masses  of  fat ;  but  after  the  most  careful  ex- 
amination, prolonged  for  two  hours,  I  failed  to  discover  any  crys- 
tals of  cholesterin.     The  appearance  is  represented  in  Fig.  2. 

The  second  examination,  eleven  days  after,  discovered  a  small 
quantity  of  cholesterin  mixed  with  the  matters  noted  in  the  first 
examination.     This  appearance  is  represented  in  Fig.  3. 

Substance  of  the  Brain. — All  the  microscopic  examinations 
of  the  extract  from  the  brain  showed  crystals  of  cholesterin  in 
large  quantity.  The  crystals  from  the  brain  are  described  by  Robin 
as  being  thinner  and  more  elongated  than  those  found  in  other 
situations.*  This  peculiarity  I  also  noticed.  The  appearance  is 
represented  in  Fig.  4. 

Blood  from  the  Internal  Jugular. — In  the  first  examination 
of  the  specimen  from  the  internal  jugular,  after  the  blood  had 
been  treated  with  ether,  the  ether  allowed  to  evaporate  and  the 
residue  extracted  with  hot  alcohol,  well-marked  plates  of  choles- 
terin were  noted.  At  this  time  it  could  not  be  discovered  in  any 
of  the  other  specimens  of  blood  after  the  most  careful  and  patient 
examination.  After  the  caustic  potash  had  been  added,  choles- 
terin was  demonstrated  in  large  quantity,  with  a  few  crystals  of 
stercorin.  The  appearance  is  represented  in  Fig.  5,  which  was 
drawn  eleven  days  after  the  blood  was  collected.  Another  exam- 
ination was  made  on  the  following  day,  which  showed,  in  addition 
to  cholesterin,  a  considerable  quantity  of  stercorin.     (See  Fig.  6.) 

Blood  from  the  Vena  Cava. — The  extract  of  the  blood  from 
the  vena  cava,  examined  eleven  days  after  the  blood  was  drawn, 
showed  a  large  quantity  of  stercorin  and  a  few  crystals  of  choles- 
terin. Cholesterin  was  distinct  but  not  very  abundant.  (See 
Fig-  7-) 

These  experiments,  the  first  that  I  made  on  this  sub- 
ject, demonstrate  the  following^  facts:  i.  That  the  brain 
contains  a  large  quantity  of  cholesterin  (which  had,  how- 
ever,   been    previously    established).      2.    That   the    blood 

*  "  Traite  de  chimie  anatomique,"  Robin  and  Verdeil,  tome  iii.,  p.  57. 


i86  NEW   FUNCTION   OF  THE    LIVER 

going  to  the  brain  contains  a  small  ([uantity  of  cholesterin, 
while  the  blood  coming  from  the  brain  contains  a  large 
quantity.  3.  That  the  blood  coming  from  the  lower  ex- 
tremities and  i^elvic  organs  contains  more  cholesterin  than 
the  blood  carried  to  them  by  the  arterial  system. 

It  was  only  necessary  to  confirm  these  statements  by 
further  investigation,  to  be  enabled  to  deduce  from  them 
the  following  important  conclusions:  That  cholesterin  is 
formed  in  some  of  the  tissues  of  the  body;  and,  judging 
from  the  fact  that  the  nervous  tissue  is  the  only  one  in 
which  it  is  found  and  that  the  blood  gains  it  in  its  passage 
through  the  great  nervous  centre,  it  is  formed  in  great 
part  by  the  nervous  system.  After  the  first  experiment, 
which  almost  confirmed  the  supposition  with  which  I  had 
started,  I  directed  my  attention  to  the  perfection  of  a  pro- 
cess by  which  I  might  make  an  accurate  quantitative  anal- 
ysis of  the  blood  for  cholesterin,  so  as  to  be  able  to  state 
positively  that  it  gained  cholesterin  in  its  passage  through 
certain  organs,  and  furthermore  to  determine  the  amount 
of  increase.  After  a  number  of  experiments  I  fixed  upon 
the  process  which  I  have  minutely  described  in  the  first 
part  of  this  article,  and  made  the  following  experiments 
for  the  purpose  of  ascertaining  the  quantity  of  cholesterin 
produced  in  the  brain: 

Experiment  IV. — A  medium-sized  adult  dog  was  put  under 
the  influence  of  ether  and  the  carotid  artery,  internal  jugular  and 
femoral  veins  exposed.  Specimens  of  blood  were  drawn,  first  from 
the  internal  jugular,  next  from  the  carotid,  and  last,  from  the 
femoral  vein.  These  specimens  were  received  into  carefully 
weighed  vessels  and  weighed. 

They  were  then  analyzed  for  cholesterin  by  the  process  already 
■described,  and  the  following  results  obtained : 

Quantity  of  blood.      Cholesterin.     Cholesterin  per 
grains.  grains.  i,ooo  pts. 

Carotid 1 79.462  o.  1 39  0.774 

Internal  jugular i34-78o  0.108  0.801 

Femoral  vein 133-886  0.108  0.806 

Percentage  of  increase  in  blood  from  the  jugular  over  the  arte- 
rial blood 3  488 

Percentage  of  increase  of  blood  from  the  femoral  vein . .    4- 1 34 

This  experiment  shows  an  increase  in  the  quantity  of 
cholesterin  in  the  blood  during  its  passage  through  the 
brain  and  an  increase,  even  a  little  greater,  in  the  blood 


NEW    FUNCTION   OF   THE    LIVER  187 

passing  through  the  vessels  of  the  posterior  extremity. 
To  faciHtate  the  operation,  however,  the  animal  was 
brought  completely  under  the  influence  of  ether,  which, 
from  its  action  on  the  brain,  would  not  improbably  pro- 
duce some  temporary  disturbance  in  the  nutrition  of  that 
organ  and  consequently  interfere  with  the  experiment.  For 
the  purpose  of  avoiding  this  difiiculty  I  performed  the  fol- 
lowing experiments  without  administering  an  anesthetic: 

Experiment  V. — A  small  young  dog  was  secured  to  the  oper- 
ating table  and  the  internal  jugular  and  the  carotid  exposed  on  the 
right  side.  Blood  was  taken,  first  from  the  jugular  and  afterward 
from  the  carotid.  The  femoral  vein  on  the  same  side  was  then 
•exposed  and  a  specimen  of  blood  taken  from  that  vessel.  The  ani- 
mal was  very  quiet  under  the  operation,  though  no  anesthetic  was 
used,  so  that  the  blood  was  drawn  without  any  difficulty  and  with- 
out the  slightest  admixture. 

The  three  specimens  were  analyzed  for  cholesterin  with  the 
following  results : 

Quantity  of  blood       Cholesterin.     Cholesterin  per 
grains.  grains.  i,ooo  pts. 

Carotid 143.625  0.679  0.967 

Internal  jugular 29.956  0.046  1-545 

Femoral  vein 45-035  0.046  i  .028 

Percentage  of  increase  in  blood  from  the  jugular  over  arterial 

blood 59-772 

Percentage  of  increase  of  blood  from  the  femoral  vein 6.308 

Experiment  VL — A  large  and  powerful  dog  was  secured  to  the 
■operating  table  and  the  carotid  and  internal  jugular  exposed. 
Specimens  of  blood  were  taken  from  these  vessels,  first  from  the 
jugular,  carefully  weighed  and  analyzed  for  cholesterin  in  the 
usual  way.     The  following  results  were  obtained : 

Quantity  of  blood.      Cholesterin.       Proportion  in 
grains.  grains.  i,ooo  pts. 

Carotid 140.847  o.  108  0.768 

Internal  jugular 97-8 1 1  0.092  0.947 

Percentage  of  increase  in  passing  through  the  brain 23.307 

Experiment  V.  shows  a  very  considerable  increase  in 
the  quantity  of  cholesterin  in  the  blood  passing  through  the 
brain,  while  it  is  comparatively  slight  in  the  blood  of  the 
femoral  vein.  The  proportion  of  cholesterin  is  also  large 
in  the  arterial  blood  as  compared  with  other  observations. 

Experiment  VI.  shows  but  a  slight  difference  in  the 
quantity  of  cholesterin  in  the  arterial  blood  in  the  two  ani- 
mals; the  proportion  in  the  animal  that  was  etherized  being 
0.774  pts.  per  1,000,  and  in  the  animal  that  was  not  ether- 


i88  NEW    FUNCTION   OF   THE    LIVER 

ized  0.768  per  1,000,  the  difference  being  but  0.006;  but, 
as  I  had  suspected,  the  ether  had  an  influence  on  the  quan- 
tity of  cholcsterin  absorbed  by  the  blood  in  its  passage 
through  the  brain.  In  the  first  instance  the  increase  was 
but  3.488  per  cent.,  while  in  the  latter  it  was  23.307.  Un- 
fortunately the  blood  was  not  taken  from  the  femoral  vein. 
I  intended  to  take  blood  from  the  abdominal  organs,  but 
after  opening  the  abdomen  the  struggles  of  the  animal 
were  so  violent  that  this  was  impossible,  and  he  was  killed. 

What  are  the  natural  conclusions,  from  the  preceding 
experiments,  in  regard  to  the  origin  of  cholesterin  in 
the  economy?  It  has  been  found  that  the  brain  and  nerves 
contain  a  large  quantity  of  this  substance,  which  is  found 
in  none  other  of  the  tissues  of  the  body.  The  preceding 
experiments,  especially  Experiments  V.  and  VI.,  show  that 
the  blood  which  comes  from  the  brain  contains  a  much 
larger  quantity  of  cholesterin  than  the  blood  which  goes 
to  this  organ. 

The  conclusion  is,  then,  that  cholesterin  is  produced  in 
the  brain  and  thence  absorbed  by  the  blood. 

But  the  brain  is  not  the  only  part  where  cholesterin 
is  produced.  It  will  be  seen  by  Experiment  IV.  that  there 
is  4.134  per  cent.,  and  in  Experiment  V.,  6.308  per  cent, 
of  increase  in  cholesterin  in  the  passage  of  the  blood 
through  the  inferior  extremities,  and  probably  about  the 
same  in  other  parts  of  the  muscular  system.  In  examining 
these  tissues  chemically,  I  find  that  the  muscles  contain 
no  cholesterin,  but  that  it  is  abundant  in  the  nerves;  and 
as  it  is  found  that  the  proportion  of  cholesterin  is  im- 
mensely increased  in  the  passage  of  the  blood  through 
the  great  centre  of  the  nervous  system,  taken,  as  the  speci- 
mens examined  were,  from  the  internal  jugular,  which 
collects  the  blood  from  the  brain  and  very  little  from  the 
muscular  system,  it  is  rendered  almost  certain,  that  in  the 
general  venous  system,  the  cholesterin  which  the  blood 
contains  is  produced  in  the  substance  of  the  nerves. 

If  this  is  true,  and  if,  as  I  hope  to  show,  cholesterin 
is  a  product  of  the  destructive  assimilation  of  nervous 
tissue,  its  production  would  be  proportionate  to  the  activ- 
ity of  the  nutrition  of  the  nerves;  and  anything  which  in- 
terfered to  any  great  extent  with  their  nutrition  would 
diminish  the  quantity  of  cholesterin   produced.      In   the 


NEW    FUNCTION    OF  THE    LIVER  189 

production  of  urea  by  the  general  system,  which  is  an  anal- 
ogous process,  muscular  activity  increases  the  quantity, 
and  inaction  diminishes  it,  on  account  of  the  efifect  upon 
nutrition.  In  cases  of  paralysis  there  is  a  diminution  of  the 
nutritive  forces  in  the  parts  affected,  especially  of  the  nerv- 
ous system,  which,  after  a  time,  becomes  so  disorganized, 
that  although  the  cause  of  the  paralysis  be  removed,  the 
nerves  can  not  resume  their  functions.  It  is  true  that  this 
exists  to  a  certain  extent  in  the  muscles;  but  it  is  by  no 
means  so  marked  as  it  is  in  the  nerves.  We  should  be  able, 
then,  to  confirm  the  observations  on  animals  by  examining 
the  blood  in  cases  of  paralysis;  when  we  should  find  a  very 
marked  difference  in  the  quantity  of  cholesterin  between 
the  venous  blood  coming  from  the  paralyzed  parts  and 
that  from  other  parts  of  the  body.  With  this  in  view  I 
made  analyses  of  the  blood  from  both  arms  in  three  cases 
of  hemiplegia,  which  seemed  to  me  most  suitable  for  such 
a  comparison: 

Case  I. — Sarah  Rumsby,  jet.  47,  affected  with  hemiplegia  of 
the  left  side.  Two  years  ago  she  was  taken  with  apoplexy  and 
was  insensible  for  three  days.  When  she  recovered  consciousness 
she  found  herself  paralyzed  on  the  left  side.  Said  she  had  epilepsy 
four  or  five  years  before  the  attack  of  apoplexy.  Now  she  has 
entire  paralysis  of  motion  on  the  affected  side,  with  the  exception 
of  some  slight  power  over  the  fingers,  but  sensation  is  perfect. 
The  speech  is  not  affected.     The  general  health  is  good. 

Case  II. — Anna  Wilson,  ?et.  23,  Irish,  affected  with  hemiplegia 
■of  the  right  side.  Four  months  ago  she  was  taken  with  apoplexy, 
from  which  she  recovered  in  one  day  with  loss  of  motion  and  sensa- 
tion on  the  right  side.  She  is  now  improving  and  can  use  the 
right  arm  slightly.  The  leg  is  not  so  much  improved  because  she 
wall  make  no  effort  to  use  it. 

Case  III.— Honora  Sullivan,  Irish,  ret.  40,  affected  with  hemi- 
plegia of  the  right  side.  About  six  months  ago  she  was  taken  with 
apoplexy  and  recovered  consciousness  the  next  day,  with  paralysis. 
The  leg  was  less  affected  than  the  arm.  from  the  first.  The  cause 
was  supposed  by  Dr.  Flint,  the  attending  physician,  to  be  due  to 
an  embolus.  Her  condition  is  now  about  the  same  as  regards  the 
arm,  but  the  leg  has  somewhat  improved. 

These  cases  all  occurred  at  the  Blackwell's  Island  Hos- 
pital. The  treatment  in  all  consisted  of  good  diet,  frictions, 
passive  motion  and  use  of  the  paralyzed  members  as  much 
as  possible. 

A  small  quantity  of  blood  was  drawn  from  both  arms 
in  these  three  cases.     It  was  drawn  from  the  paralyzed 


190 


NEW    FUNCTION   OF  THE    LIVER 


side,  in  each  instance,  with  great  difficulty,  and  but  a  small 
quantity  could  be  obtained. 

The  specimens  were  all  examined  for  cholesterin,  with 
the  following  results: 

Table  of  Quantity  of  Cholesterin  in  Blood  of  Paralyzed  and 
Sound  Sides  in  Three  Cases  of  Hemiplegia 


Blood. 

Cholesterin. 

Cholesterin  per  1,000. 

Case      I.   Paralyzed  side.  .  .  . 

grains. 

55-458 

grains. 

The  watch-glass  contained 
0.031  grain  of  a  sub- 
stance, but  the  most  care- 
ful examination  failed  to 
show  a  single  crystal  of 
cholesterin. 

"         Sound  side 

128.407 

0.062 

0.481. 

Case    II.  Paralyzed  side. .  .  . 
"          Sound  side 

18.381 
66.396 

0.062 

Same  as  Case  I. 
0.808. 

Case  III.  Paralyzed  side 

21.84a 

Same  as  Case  I. 

"          Sound  side 

52.261 

0.031 

0.579- 

The  result  of  these  examinations  is  very  interesting: 
not  a  single  crystal  of  cholesterin  was  found  in  any  of  the 
three  specimens  of  blood  from  the  paralyzed  side,  while 
about  the  normal  quantity  was  found  in  the  blood  from 
the  sound  side.  As  the  nutrition  of  other  tissues  is  inter- 
fered with  in  paralysis,  it  is  impossible  to  say  positively, 
from  these  observations  alone,  that  cholesterin  is  produced 
in  the  nervous  system  only.  But  the  nutrition  of  the  nerves 
is  undoubtedly  most  affected;  and  this  observation,  taken 
in  connection  with  the  preceding  experiments  on  animals,, 
seems  to  settle  where  cholesterin  is  produced. 

I  may  extend  my  first  conclusion,  then,  and  state  that 
cholesterin  is  produced  in  the  substance  of  the  nervous 
system. 

Before  entering  upon  the  character  of  cholesterin  and 
inquiring  whether  it  is  an  excrementitious  or  recrementi- 
tious  product,  I  shall  endeavor  to  follow  it  out  in  the  sys- 
tem and  ascertain  if  there  is  any  organ  which  separates 
it  from  the  blood.  In  pursuing  this  question,  the  method 
will  be  adopted  that  has  been  employed  in  investigating- 
its  origin;  that  is.  analyzing  the  blood  as  it  goes  to  and 
comes  from  certain  organs.     The  organ  which  one  would 


NEW    FUNCTION   OF  THE    LIVER  191 

be  led  first  to  examine  is  the  liver,  as  it  is  the  only  gland 
the  product  of  which  contains  cholesterin,  which,  if  not 
manufactured  in  the  gland  itself,  must  be  separated  from 
the  blood. 

In  the  first  series  of  experiments  which  I  performed  on 
this  subject,  I  endeavored  to  show  on  the  same  animal 
the  origin  of  cholesterin  in  certain  parts  and  its  removal 
from  the  body.  In  these  experiments — in  which  the  results 
were  approximative,  as  I  had  not  succeeded  in  extract- 
ing cholesterin  perfectly  pure — I  began  with  the  arterial 
blood,  examining  it  as  it  went  into  the  brain  by  the  carotid, 
analyzing  the  substance  of  the  brain;  then  analyzing  the 
blood  as  it  came  out  of  the  brain  by  the  internal  jugular;  ex- 
amining the  blood  as  it  went  into  the  liver  by  the  hepatic 
artery  and  portal  vein;  examining  the  secretion  of  the 
liver;  then  the  blood  as  it  came  out  of  the  liver  by  the 
hepatic  vein;  examining  also  the  blood  of  the  vena  cava 
in  the  abdomen.  The  analyses  of  the  blood  from  the 
carotid,  internal  jugular,  and  vena  cava  have  already 
been  referred  to,  in  treating  of  the  origin  of  cholesterin. 
It  will  be  remembered  that  there  was  a  large  quantity  of 
this  substance  in  the  internal  jugular,  and  but  a  small  quan- 
tity in  the  carotid,  showing  that  it  was  formed  in  the  brain. 
I  now  give  the  conclusion  of  those  observations,  which 
bears  upon  the  separation  of  cholesterin  from  the  blood. 

Experiment  VII. — Specimens  of  blood  were  taken  from  the 
hepatic  artery,  portal  vein  and  hepatic  vein,  and  a  small  quantity 
of  bile  from  the  gall-bladder.  These  specimens  were  treated  in 
the  manner  already  indicated  in  Experiment  III.;  i.  e..  evaporated 
and  pulverized,  extracted  with  ether,  the  ether  evaporated,  and  the 
residue  extracted  with  boiling  alcohol,  this  evaporated,  a  solution 
of  caustic  potash  added  and  then  subjected  to  a  microscopic  exam- 
ination. 

Blood  from  the  Portal  Vein. — Microscopic  examination  of 
the  extract  from  the  portal  vein  showed  quite  a  number  of  crystals 
of  cholesterin,  which  are  represented  in  Fig.  8.  These  were  ob- 
served after  the  fluid  had  nearly  evaporated. 

Blood  from  the  Hepatic  Artery. — Microscopic  examination 
of  the  extract  from  the  hepatic  artery,  made  after  the  fluid  had 
nearly  evaporated,  showed  a  considerable  quantity  of  cholesterin, 
more  than  was  observed  in  the  preceding  specimen.  (See  Fig.  9.) 
There  were  also  observed  a  few  crystals  of  stercorin,  represented 
in  Fig.  10. 

Blood  from  the  Hepatic  Vein. — The  first  examination  of  the 
extract  from  the  hepatic  vein,  which  was  made  just  before  the 


192  NEW   FUNCTION  OF  THE    LIVER 

potash  was  added,  showed  a  number  of  fatty  masses  with  some 
crystals  of  stercorin.  The  solution  of  potash  was  then  added,  and 
two  (lays  after,  another  careful  examination  was  made,  discovering 
nothing  but  fatty  globules  and  granules.  (See  Fig.  ii.)  The 
watch-glass  was  then  set  aside  and  was  examined  eleven  days 
after,  when  the  fluid  had  entirely  evaporated.  At  this  examination 
a  few  crystals  of  cholesterin  were  observed  for  the  first  time.  (See 
Fig.  12.)  There  were  also  a  number  of  crystals  of  margaric  and 
of  stearic  acid. 

Bile. — All  the  examinations  of  the  extract  from  the  bile 
showed  cholesterin ;  the  precipitate  consisted,  indeed,  of  this  sub- 
stance in  a  nearly  pure  state.  Fig.  13  represents  some  of  the  crys- 
tals which  were  observed  in  this  specimen. 

Considering  this  series  of  experiments  in  connection 
with  the  first  observations  on  the  carotid  and  internal  jugu- 
lar, while  the  one  series  demonstrates  pretty  conclusively 
that  cholesterin  is  formed  in  the  brain,  the  other  shows 
that  it  disappears,  in  a  measure,  from  the  blood  in  its  pas- 
sage through  the  liver  and  is  found  in  the  bile.  In  other 
words,  it  is  formed  in  the  nervous  tissue  and  prevented 
from  accumulating  in  the  blood  by  its  excretion  by  the 
liver.  This  suggests  an  interesting  series  of  inquiries;  and 
this  fact,  if  substantiated,  would  be  as  important  to  the  pa- 
thologist as  to  the  physiologist.  But  in  order  to  settle  this 
important  question,  it  is  necessary  to  do  something  more 
than  make  an  approximate  estimate  of  the  quantity  of 
cholesterin  removed  from  the  blood  by  the  liver.  The 
cjuantity  which  is  thus  removed  in  the  passage  of  the  blood 
through  this  organ  should  be  estimated,  if  possible,  as 
closely  as  the  quantity  which  the  blood  gains  in  its  passage 
through  the  brain.  But  this  estimate  is  more  difficult. 
The  operation  for  obtaining  the  blood,  in  the  first  place, 
is  much  more  serious  than  that  for  obtaining  blood  from 
the  carotid  and  internal  jugular.  It  is  very  difficult  to  ob- 
tain the  unmixed  blood  from  the  hepatic  vein;  and  the 
exposure  of  the  liver,  if  prolonged,  must  interfere  with  its 
eliminative  function,  in  the  same  way  that  exposure  of  the 
kidneys  arrests  in  a  few  moments  the  flow  from  the  ureter. 
It  is  probable,  however,  that  the  administration  of  ether 
does  not  interfere  with  the  elimination  of  cholesterin  by 
the  liver  as  it  does  apparently  with  its  formation  in  the 
brain.  Anesthetics  have  a  peculiar  and  special  action 
on  the  brain,  but  they  do  not  interfere  with  the  functions 
of  vegetative  life,  like  secretion  or  excretion;  and  there- 


NEW    FUNCTION   OF  THE    LIVER 


193 


fore  they  would  not  interfere  with  the  depurative  function 
of  the  Hver.  It  is  fortunate  that  this  is  the  case,  for  the 
operation  of  taking  blood  from  the  abdominal  vessels  is 
immensely  increased  in  difficulty  by  the  struggles  of  an 
animal  not  under  the  influence  of  an  anesthetic,  so  much 
so,  indeed,  that  I  failed  entirely  in  obtaining  any  blood 
from  one  animal  (the  one  used  in  Experiment  VI.),  which 
was  not  etherized.  It  was  a  very  powerful  dog,  and  his 
•struggles  were  so  violent  that  it  was  impossible  to  collect 
the  blood  accurately  from  the  abdominal  vessels  and  the 
attempt  was  abandoned.  With  the  view  of  settling  the 
question  of  the  disappearance  of  a  portion  of  the  choles- 
terin  of  the  blood  in  its  passage  through  the  liver,  by  an 
accurate  quantitative  analysis,  I  repeated  the  operation  for 
drawing  blood  from  the  vessels  which  go  into  and  emerge 
from  the  liver.  In  my  first  trial  the  blood  was  drawn  so 
unsatisfactorily  and  the  operation  was  so  prolonged,  that 
I  did  not  think  it  worth  while  to  complete  the  analysis  and 
abandoned  the  experiment.  In  the  following  one  I  was 
more  successful: 

Experiment  VIII. — A  good-sized  bitch  (pregnant)  was 
brought  completely  under  the  influence  of  ether,  the  abdomen  laid 
freely  open,  and  blood  drawn  first  from  the  hepatic  vein,  and  next 
from  the  portal  vein.  The  taking  of  the  blood  was  entirely  satis- 
factory, the  operation  being  done  rapidly  and  the  blood  collected 
without  any  admixture.  A  specimen  of  blood  was  then  taken  from 
the  carotid  to  represent  the  blood  from  the  hepatic  artery. 

The  three  specimens  of  blood  were  then  examined  in  the  usual 
way  for  cholesterin,  with  the  following  results : 

Quantity  of  blood.      Cholesterin.      Cholesterin  in 
grains.  grains.  1,000  pts. 

Arterial  blood 159-537  0200  1  —  57 

Portal  vein 168.257  0.170  1.009 

Hepatic  vein 79-848  0.077  0.964 

Percentage  of  loss  in  arterial  blood  in  its  passage  through  the 

liver 23.309 

Percentage  of  loss  in  blood  of  the  portal  vein 4.460 

This  experiment  proves  positively  what  there  was  good 
ground  for  supposing  from  Experiment  VII.;  namely,  that 
cholesterin  is  separated  from  the  blood  by  the  liver;  and 
here  I  may  note,  in  passing,  a  striking  coincidence  be- 
tween the  analysis  in  Experiment  VI.,  when  the  blood  was 
studied  in  its  passage  through  the  brain,  and  the  one  just 
mentioned,  when  the  blood  was  studied  in  its  passage 
13 


194  NEW    FUNCTION   OF  THE    LIVER 

through  the  H\'er.  The  gain  of  the  arterial  blood  in  cho- 
lesterin  in  passing  through  the  brain  was  23.307  per  cent., 
and  the  loss  of  this  substance  in  passing  through  the  liver 
is  23.309  per  cent.  There  must  be,  of  course,  the  same 
quantity  sei)arated  by  the  liver  that  was  formed  by  the 
nervous  system,  it  being  formed,  indeed,  only  to  be  sepa- 
rated by  this  organ,  its  formation  being  continuous,  and 
its  removal  necessarily  the  same,  in  order  to  prevent  its 
accumulation  in  the  circulating  fluid.  The  almost  ex- 
act coincidence  between  these  two  quantities,  in  speci- 
mens taken  from  different  animals,  though  not  at  all 
necessary  to  prove  the  fact  just  mentioned,  is  still  very 
striking. 

It  is  shown  by  Experiment  VIII.  that  the  portal  blood, 
as  it  goes  into  the  liver,  contains  but  a  small  percentage 
of  cholesterin  over  the  blood  of  the  hepatic  vein,  while 
the  percentage  in  the  arterial  blood  is  large.  The  arterial 
blood  is  the  mixed  blood  of  the  entire  system;  and  as  it 
probably  passes  through  no  organ  before  it  gets  to  the 
liver,  which  diminishes  its  cholesterin,  it  contains  a  quantity 
of  this  substance  which  must  be  removed.  The  portal 
blood,  coming  from  a  limited  part  of  the  system,  contains 
less  of  this  substance,  though  it  gives  up  a  certain  quan- 
tity. In  the  circulation  in  the  liver,  the  portal  system 
largely  predominates,  and  is  necessary  to  other  important 
functions  of  this  organ,  such  as  the  production  of  gly- 
cogen. Soon  after  the  portal  vein  enters  the  liver,  its 
blood  becomes  mixed  with  that  from  the  hepatic  artery,* 
and  from  this  mixture  cholesterin  is  separated.  It  is  only 
necessary  that  blood,  containing  a  certain  quantity  of  cho- 
lesterin, should  come  in  contact  with  the  bile-secreting" 
cells,  for  this  substance  to  be  separated.  The  fact  that 
it  is  eliminated  by  the  liver  is  proved  with  much  less  dififi- 
culty  than  that  it  is  formed  in  the  nervous  system.  In 
fact,  its  presence  in  the  bile,  the  necessity  for  its  constant 
removal  from  the  blood,  which  is  consequent  on  its  con- 
stant formation  and  absorption  by  this  fluid,  are  almost 

*  According  to  Robin,  the  branches  of  the  hepatic  arter}'  are  distributed 
almost  entirely  in  the  interlobular  plexuses  and  on  the  walls  of  the  hepatic  duct 
and  portal  vein  and  do  not  find  their  way  into  the  substance  of  the  lobules. — 
"  Dictionnaire  de  medecine,  de  chirurgie,  de  pharmacie,  des  sciences  acces- 
soires  et  de  I'art  vdterinaire,"  P.  H.  Nysten  ;  "  onzieme  edition  revue  et  cor- 
rige."     Par  E.  Littre  et  Ch.  Robin.     Paris,  1858.     Article  "  Foie." 


NEW    FUNCTION    OF  THE    LIVER  195 

sufficient  in  themselves  to  warrant  the  conchision  that  it 
is  removed  by  the  hver.  This,  however,  is  put  beyond  a 
doubt  by  the  preceding  analysis  of  the  blood  going  to  and 
coming  from  this  organ. 

Another  link,  then,  is  added  to  the  chain  of  facts  which 
make  up  the  history  of  cholesterin.     The  first  is  that — 

Cholesterin  is  formed  in  the  brain  and  nervous  system 
and  is  absorbed  by  the  blood. 

The  second,  which  has  just  been  proved,  is  that — 

Cholesterin,  formed  in  these  situations  and  absorbed 
by  the  blood,  is  separated  from  the  blood  in  its  passage 
through  the  liver. 

The  next  question,  in  following  out  this  line  of  inquiry, 
is,  what  becomes  of  the  cholesterin  which  is  separated  from 
the  blood?  This  question  is  very  easily  answered,  and 
necessitates  only  an  examination  of  one  of  the  products 
of  the  liver,  the  bile. 

Bile. — In  the  few  remarks  with  which  I  prefaced  this 
article,  I  spoke  of  the  various  opinions  which  are  held 
by  physiologists  with  reference  to  the  function  of  the 
bile;  some  regarding  it  as  purely  excrementitious,  others 
placing  it  among  the  recrementitious  fluids.  I  detailed 
experiments  which  led  me  to  think  that  it  had  two  distinct 
functions:  one,  which  is  recrementitious  and  is  probably 
concerned  in  digestion  to  an  important  degree,  but  which 
it  is  not  designed  to  take  up  in  this  connection;  the  other, 
which  is  excrementitious,  and  which  is  necessarily  taken 
up  in  a  discussion  of  the  important  substance  now  under 
consideration.  A  glance  at  the  composition  of  the  bile 
will  show  that  it  is  an  exceedingly  complex  fluid;  and 
physiological  investigations  into  the  destination  of  certain 
of  its  ingredients,  by  Bidder  and  Schmidt,  Dalton  and 
others,  have  shown  that  they  are  not  discharged  from  the 
body,  but  reabsorbed  by  the  blood;  though  the  failure  to 
detect  them  in  the  portal  blood  by  the  appropriate  tests 
shows  that  in  this  reabsorption  they  probably  undergo  some 
alteration.*  These  substances,  which  have  heretofore  been 
considered  as  the  most  important  ingredients  of  the  bile, 

*  For  a  very  complete  account  of  the  bile,  with  original  investigations  into 
the  destination  of  the  biliary  salts,  the  reader  is  referred  to  an  article  published 
by  Prof.  John  C.  Dalton,  Jr.,  in  the  "American  Journal  of  the  Medical  Sci- 
ences," October,  1857,  and  the  chapter  on  bile  in  Dalton's  "Physiology." 


196  NEW    FUNCTION    OF  THE    LIVER 

though  their  function  is  obscure,  are  the  glycocholate  and 
taurocholate  of  soda,  discovered  by  Strecker  in  the  bile  of 
the  ox,  in  1848.  The  following  is  the  composition  of  the 
bile  given  in  Dalton's  "  Physiology,"  which  is  "  based  on 
the  calculations  of  Berzclius,  Frerichs  and  Lehmann."  * 

Composition  of  Ox  Bile 

Water 880.00 

Glycocholate  of  soda }     go  00 

Taurocholate  of  soda f     ^' 

Biliverdin 1 

Fats    (      J  -  .  2 

Oleates,  margarates  and  stearates  of  soda  and  potassa. .  {       -^'^ 

Cholesterin J 

Chloride  of  sodium 1 

Phosphate  of  soda | 

Phosphate  of  lime [     1 5.24 

Phosphate  of  magnesia | 

Carbonates  of  soda  and  potassa J 

Mucus  of  the  gall-bladder i  .34 

1 ,000.00 

Of  the  above  ingredients  of  the  bile,  are  biliverdin, 
which  is  simply  a  coloring  matter;  fats,  with  oleates,  mar- 
garates and  stearates,  which,  with  the  biliary  salts,  are  said 
to  hold  the  cholesterin  in  solution;  chloride  of  sodium,  pres- 
ent in  all  the  animal  fluids;  phosphates  and  carbonates, 
which  are  simple  excreted  and  are  also  ingredients  of  the 
urine;  leaving,  as  the  most  important  constituents,  of  which 
the  function  is  least  understood,  the  biliary  salts  and  cho- 
lesterin. The  biliary  salts  are  probably  recrementitious; 
but  cholesterin  is  one  of  the  products  of  the  waste  of  the 
system.  The  bile,  then,  presents  the  combined  character, 
so  far  as  its  chemical  composition  is  concerned,  of  a  secre- 
tion and  of  an  excretion.  I  may  now  contrast  these  two 
properties  and  see  what  this  fluid  has  in  common  with  the 
secretions  and  how  it  obeys  the  laws  which  regulate  the 
excretions.  In  doing  this  I  shall  first  contrast  some  of  the 
important  distinctions  between  these  two  classes  of 
products. 

Secretions  are  characterized  by  certain  constituents 
which  are  formed  in  the  substance  of  the  gland  and  are 
found  in  no  other  situation.  Such  is  the  pancreatin  of 
the  pancreatic  juice,  the  pepsin  of  the  gastric  juice,  the 

*  Dalton's  "  Physiology,"  second  edition,  p.  158. 


NEW   FUNCTION    OF  THE    LIVER  197 

ptyalin  of  the  saliva,  and,  I  may  add,  the  glycocholate  and 
the  taurocholate  of  soda  of  the  bile. 

These  substances  first  make  their  appearance  in  the 
substance  of  the  gland  itself;  they  do  not  preexist  in  the 
blood;  they  are  discharged  from  the  gland  for  a  special 
purpose,  and  when  there  is  no  necessity  for  their  action, 
the  discharge  does  not  take  place.  Illustrations  of  this  are 
to  be  found  in  the  digestive  fluids,  which  are  true  secre- 
tions; poured  out  only  when  this  function  is  called  into 
action  by  the  ingestion  of  food,  and  not  discharged  from 
the  body,  but  their  elements  taken  up  again  by  the  blood 
when  their  function  has  been  accomplished.  Thus  the  gas- 
tric and  pancreatic  fluids  are  never  secreted  until  food  is 
taken  into  the  alimentary  canal,  and  are  reabsorbed  with 
the  digested  matters. 

The  flow  of  the  secretions  is  intermittent,  and  the  gland, 
during  the  period  of  repose,  manufactures  the  elements  of 
the  secretion,  which  are  washed  out  at  the  duct  when  the 
appropriate  stimulus  (of  food,  for  example)  causes  a  de- 
termination of  blood  to  the  organ.  The  gland  manufac- 
tures the  elements  of  the  secretion,  and  the  blood  furnishes 
the  menstruum,  the  water,  by  means  of  which  they  are  dis- 
solved and  emptied  into  the  duct.  When  the  pancreas  of 
an  animal  is  exposed  during  the  intervals  of  digestion,  it 
is  pale  and  bloodless;  no  fluid  flows  from  the  duct;  but 
the  elements  of  the  pancreatic  juice  are,  nevertheless,  in 
the  gland;  for  they  may  be  dissolved  out  from  the  gland, 
and  an  artificial  pancreatic  juice  results  which  will  have 
all  the  reactions  and  digestive  properties  of  the  natural 
secretion.  But  if  the  pancreas  of  an  animal  is  exposed 
during  digestion,  the  gland  is  turgid  with  blood;  the  secre- 
tion flows  from  the  duct,  and  the  products  of  the  gland 
are  being  washed  out  by  the  blood — a  process  which  is 
imitated  when  they  are  dissolved  out  by  maceration  in 
water.  The  late  brilliant  experiments  of  Bernard  have 
shown  that  the  function  of  the  glands  is  regulated  by  the 
nervous  system,  and  that  faradization  of  certain  nerves,  by 
which  the  nervous  force  is  imitated,  will  cause  a  determi- 
nation of  blood  to  the  organ  and  induce  secretion,  while 
stimulation  of  other  nerves  will  contract  the  vessels  and 
arrest  secretion. 

The  substances  which  characterize  the  secretions,  as 


198  NEW    FUNCTION    OF  THE    LIVER 

they  are  manufactured  in  the  "lands  and  do  not  preexist 
in  the  blood,  do  not  accumulate  in  the  blood  when  the 
gland  is  removed  or  its  functions  are  interfered  with. 

The  distinctive  characters  of  the  secretions,  in  fact,  may 
be  summed  up  thus: 

Their  elements  first  appear  in  the  glands  and  do  not 
preexist  in  the  blood.  They  are  not  discharged  from  the 
body,  with  the  exception  of  the  milk,  which  is  destined 
for  the  nourishment  of  the  child.  Their  flow  is  inter- 
mittent. They  are  destined  to  assist  in  some  of  the  nutri- 
tive functions  of  the  body. 

Excretions,  of  which  the  urine  may  be  taken  as  a  type, 
have  entirely  different  characteristics: 

Excrementitious  substances  do  not  first  make  their  ap- 
pearance in  the  organs  which  separate  them,  but  are  pro- 
duced in  the  general  system. 

They  preexist  in  the  blood,  having  been  absorbed  by 
this  fluid  from  the  parts  of  the  system  in  which  they  are 
formed,  are  carried  to  particular  organs  and  are  separated 
from  the  blood  for  the  sole  purpose  of  being  expelled  from 
the  body.  An  illustration  of  this  is  to  be  found  in  urea, 
which  has  been  detected  in  the  blood  and  urine  and  some 
of  the  tissues  of  the  body.  This  substance,  one  of  the  most 
important  excrementitious  products,  is  absorbed  by  the 
blood  from  certain  parts  of  the  system,  carried  to  the  kid- 
neys, there  separated  from  the  blood  and  discharged  from 
the  body.  Although  the  gastric  and  pancreatic  fluids,  and 
all  the  secretions  proper,  are  reabsorbed  with  the  food  after 
they  have  acted  upon  it,  urea  may  remain  any  length  of 
time  in  the  bladder,  but  it  is  never  absorbed. 

The  flow  of  the  excretions  is  constant.  No  period  of 
repose  is  necessary  for  the  gland  to  manufacture  their  ele- 
ments, as  they  all  preexist  in  the  blood.  Nutrition  is  con- 
stant, and  destructive  assimilation,  or  waste,  which  neces- 
sitates nutrition  or  repair,  is  likewise  constant.  The  blood 
supplies  all  the  wants  of  the  system  and  receives  all  the 
products  of  its  decay.  As  the  blood  is  continually  being 
impoverished,  it  must  be  regenerated  from  without;  and 
this  is  done  by  food,  which  is  prepared  for  absorption  by 
digestion.  The  secreted  fluids  are  chiefly  concerned  in 
digestion;  and  as  this  is  an  occasional  process,  the  secre- 
tions are  intermittent.      But  waste  is   continually  going 


NEW   FUNCTION   OF   THE    LIVER  199 

on  and  excrementitious  substances  are  continually  form- 
ing; and  while  the  necessity  for  the  secretions  is  occasional, 
the  necessity  for  the  excretions  is  constant.  Though  the 
actual  discharge  of  the  latter  from  the  body  is  occasional, 
they  are  constantly  being  separated  from  the  blood,  and 
accumulate  in  receptacles,  whence  they  are  discharged  at 
appropriate  intervals.  No  such  receptacles  exist  for  the 
secretions  proper,  except  in  the  instance  of  the  milk,  which 
accumulates  in  the  ducts  of  the  mammary  gland  and  is 
the  only  secretion  which  is  discharged  from  the  body. 

If  the  secreting  glands  take  on  an  excretory  function, 
as  is  an  occasional  pathological  occurrence,  their  flow  be- 
comes continuous.  An  example  of  this  is  the  occasional 
separation  of  urea  from  the  blood  by  the  gastric  tubules. 
When  the  kidneys  become  so  affected  by  disease  as  to  be 
unable  to  separate  the  urea  from  the  system,  the  accumu- 
lation of  this  excretion  in  the  blood  frequently  induces  other 
organs  to  attempt  its  removal.  The  gastric  tubules  take 
on  this  function  and  produce  a  fluid  which  contains  urea. 
The  gastric  juice,  if  I  may  now  so  term  it,  is  no  longer 
a  secretion  but  an  excretion;  and  its  flow  is  no  longer 
intermittent  and  dependent  upon  the  stimulus  of  food  in- 
troduced into  the  stomach,  but  is  constant,  and  continues 
until  the  irritation  caused  by  the  decomposing  urea  in  the 
stomach  induces  an  inflammation  which  prevents  further 
secretion.  This  is  an  example  of  an  intermittent  secretion, 
characterized  by  a  substance  manufactured  in  the  gland 
and  not  preexisting  in  the  blood,  changed  into  a  constant 
excretion,  characterized  by  a  substance  which  is  not  manu- 
factured in  the  gland  but  preexists  in  the  blood. 

The  substances  which  characterize  the  excretions  accu- 
mulate in  the  blood  when  the  organ  which  eliminates  them 
is  removed  or  its  functions  are  interfered  with.  It  is  this 
fact  which  led  to  a  knowledge  that  urea  preexisted  in  the 
blood.  It  was  detected  in  that  fluid  when  it  had  accumu- 
lated in  animals  from  which  the  kidneys  had  been  removed, 
and  in  cases  of  Bright's  disease  of  the  kidneys,  before 
chemical  processes  were  sufficiently  delicate  to  detect  it 
in  healthy  blood,  when  the  quantity  is  kept  down  by  its 
constant  elimination  by  the  kidneys. 

The  characters  of  the  excretions,  then,  are  entirely  op- 
posite to  those  of  the  secretions. 


200  NEW    FUNCTION   OF  THE    LIVER 

Their  elements  preexist  in  the  blood  and  are  not  manu- 
factured in  the  substance  of  the  organs  which  eliminate 
them.  Their  flow  is  constant.  They  are  separated  from 
the  blood  merely  to  be  discharged  from  the  body  and  are 
not  destined  to  assist  in  any  of  the  nutritive  functions. 

Having  contrasted  the  secretions  and  the  excretions,. 
I  shall  now  examine  the  bile  and  note  what  are  the  char- 
acters which  it  has  in  common  with  either  or  both  of  these 
products. 

The  bile  is  characterized  by  two  kinds  of  constituents: 
One  of  them,  the  glycocholate  and  the  taurocholate  of 
soda,  manufactured  in  the  liver,  found  in  no  other  fluid  than 
the  bile,  does  not  preexist  in  the  blood,  and  associates  the 
bile  with  the  secretions.  The  other,  the  cholesterin,  pre- 
exists in  the  blood  and  is  simply  separated  from  it  by  the 
liver,  giving  the  bile  one  of  the  characters  of  an  excretion. 

The  biliary  salts  (the  glycocholate  and  taurocholate 
of  soda)  are  discharged  into  the  intestinal  canal  for  a  spe- 
cial purpose;  and  this  discharge  takes  place  at  the  begin- 
ning of  the  digestive  act.  If  the  liver  and  gall-bladder 
of  a  dog  which  has  not  taken  food  is  exposed,  the  gall- 
bladder will  be  found  distended  with  bile;  but  if  these  or- 
gans are  examined  when  digestion  is  going  on,  the  gall- 
bladder will  be  found  nearly  empty.  It  is  true  that  after 
prolonged  fasting  the  bile  is  discharged  into  the  alimen- 
tary canal,  but  it  must  be  remembered  that  it  contains 
another  ingredient,  cholesterin,  which  must  be  discharged 
from  the  body,  as  will  appear  presently.  The  biliary  salts 
are  not  discharged  from  the  body.  Dr.  Dalton  has  shown 
that  the  substances  extracted  from  the  contents  of  the 
large  intestine  by  evaporation,  extraction  of  the  residue 
with  alcohol  and  precipitation  with  ether,  will  not  react 
with  Pettenkofer's  test,  which  is  a  very  delicate  test  for 
the  biliary  salts.  I  have  treated  the  feces  of  the  human 
subject  in  the  same  way  with  the  same  result.  These  salts, 
therefore,  are  not  discharged  from  the  body  unchanged. 
The  next  question  to  determine  is  whether  they  are  dis- 
charged from  the  body  in  a  modified  form.  They  contain 
a  certain  quantity  of  sulphur,  of  which,  as  has  been  shown 
by  Bidder  and  Schmidt,  only  one-fifteenth  part  of  the  en- 
tire quantity  which  enters  the  intestine  with  the  bile  can 
be  detected  in  the  feces.    As  sulphur  is  an  elementary  sub- 


NEW   FUNCTION  OF  THE    LIVER  201 

stance,  it  can  not  be  decomposed;  and  the  biliary  salts,  in 
their  passage  down  the  alimentary  canal,  mnst  be  absorbed. 
It  is  true  that  these  salts  can  not  be  detected  in  the  blood 
coming  from  the  intestines,  but  we  can  not  detect  the  pan- 
creatin  of  the  pancreatic  juice,  the  pepsin  or  the  acid 
of  the  gastric  juice  in  the  portal  blood,  yet  these  are  ab- 
sorbed by  the  mucous  membrane  of  the  intestinal  tube, 
changed  by  their  union  with  the  matters  they  have  di- 
gested. It  is  probable  that  an  analogous  change  takes 
place  in  the  glycocholate  and  taurocholate  of  soda,  which 
prevents  them  from  being  detected  in  the  blood  by  the 
ordinary  tests.  These  facts,  also,  place  the  bile  among  the 
secretions. 

On  the  other  hand,  cholesterin  preexists  in  the  blood, 
having  been  absorbed  by  this  fluid  from  certain  parts  of 
the  system,  is  carried  to  the  liver  and  there  separated  for 
the  sole  purpose  of  being  discharged  from  the  body.  The 
same  general  remarks  apply  to  this  substance  as  to  urea. 
This  places  the  bile  among  the  excretions. 

The  flow  of  the  secretions  is  intermittent.  This  is  not 
absolutely  true  of  the  bile,  but  the  discharge  of  this  fluid 
is  remittent.  Dr.  Dalton  *  has  reported  a  series  of  inter- 
esting experiments  upon  an  animal  with  a  duodenal  fistula. 
In  this  observation  ten  grains  of  dry  biliary  matter  were 
discharged  into  the  duodenum  of  a  dog  w^eighing  thirty- 
six  and  a  half  pounds,  immediately  after  feeding.  At  the 
end  of  the  first  hour  it  had  fallen  to  four  grains;  it  con- 
tinued at  three  and  a  half  to  four  and  a  half  grains  up  to 
the  eighteenth  hour,  when  the  quantity  was  inappreciable; 
at  the  twenty-first  hour  it  was  one  grain;  the  twenty-fourth, 
three  and  a  quarter  grains;  and  the  twenty-fifth,  three 
grains.  The  fluid  was  drawn  for  fifteen  minutes  each  time, 
evaporated  to  dryness,  extracted  with  absolute  alcohol, 
precipitated  with  ether,  the  ether  precipitate  dried  and 
weighed  as  representing  the  quantity  of  biliary  matter 
present.  These  experiments  apply  to  the  time  when  the 
bile  is  discharged  into  the  intestine;  but  as  most  animals 
have  a  gall-bladder,  which  collects  the  bile  as  it  is  secreted, 
it  does  not  show  when  this  fluid  is  formed  by  the  liver. 
Schwann,  Bidder  and  Schmidt,  Arnold,  Kolliker  and  Miil- 

*  Dalton,  "  Constitution  and  Physiology  of  the  Bile."     Loc.  cit. 


NEW   FUNCTION    OF  THE    LIVER 


ler,  have  made  experiments  bearing;-  upon  the  latter  point, 
bv  ligating-  the  ductus  communis  choledochus  and  making 
a  fistula  into  the  fundus  of  the  gall-bladder.  The  experi- 
ments of  these  observers  vary  somewhat  in  regard  to 
the  time  when  the  secretion  of  the  bile  is  at  its  maximum. 
In  the  animal  already  referred  to,  in  which  a  fistula  was 
made  into  the  fundus  of  the  gall-bladder,  the  bile  was 
collected  for  thirty  minutes  immediately  after  feeding,  one 
hour  after,  and  then  at  intervals  of  two  hours  during  the 
remainder  of  the  twenty-four  hours.  The  specimens  of  bile 
thus  collected  were  carefully  weighed,  evaporated  to  dry- 
ness and  the  proportion  of  dry  residue  taken.  The  fol- 
lowing table  shows  the  results  of  these  observations,  which 
were  made  twelve  days  after  the  operation,  when  the  ani- 
mal, which  weighed  originally  twelve  pounds,  had  lost  two 
pounds.  His  appetite  was  ravenous  at  the  time  of  the 
experiment. 

Table  of  the  Variations  of  the  Bile  in  the  Twenty-four 
Hours.  At  each  observation  the  bile  was  drawn  for  precisely  thirty 
minutes.  Dog  with  a  fistula  into  the  gall-bladder.  Weight  ten 
pounds. 


Time  after  Feeding. 


Immediately 

One  hour 

Two  hours 

Four  hours 

Six  hours 

Eight  hours 

Ten  hours 

Twelve  hours 

Fourteen  hours.  . . . 

Sixteen  hours 

Eighteen  hours.  .  .  . 

Twenty  hours 

Twenty-two  hours. 
Twenty-four  hours 


Fresh  bile. 

Dried  bile. 

Percentage  of 
dry  residue. 

grains. 

grains. 

8.103 

0.370 

4.566 

20.527 

0.586 

2 

854 

35 • 760 

1.080 

3 

023 

38.939 

1.404 

3 

605 

22 . 209 

0.987 

4 

450 

36.577 

1.327 

3 

628 

24.447 

O.S33 

3 

407 

5.710 

6.247 

4 

325 

5.000 

0.170 

3 

400 

8.643 

0.309 

3 

575 

9.970 

0.277 

2 

778 

4  769 

0.170 

3 

565 

7.578 

0.293 

3 

866 

15.001 

0.885 

5 

233 

This  table  shows  a  regular  increase  in  the  quantity  of 
bile  discharged  from  the  fistula  from  the  time  of  feeding 
up  to  four  hours  after.  It  diminished  at  the  sixth  hour, 
rose  again  at  the  eighth  hour,  but  then  gradually  dimin- 
ished to  the  fourteenth  hour.  There  was  then  a  slight 
increase  the  sixteenth  and  eighteenth  hours,  and  the  twen- 


NEW   FUNCTION    OF  THE    LIVER  203 

tieth  hour  it  fell  to  its  minimum.  It  then  increased  slight- 
ly the  twenty-second  hour,  and  mounted  considerably  the 
twenty-fourth  hour,  when  the  observations  were  concluded. 
Disregarding  slight  variations  in  the  quantity,  which  might 
be  accidental,  it  may  be  stated  in  general  terms  that  the 
maximum  flow  of  bile  from  the  liver  is  from  the  second 
to  the  eighth  hour  after  feeding,  during  which  time  it  is 
about  stationary.  In  this  experiment  it  was  at  its  mini- 
mum the  twentieth  hour  after  feeding.  This  observation 
agrees  with  those  of  Bidder  and  Schmidt  as  regards  the 
time  when  the  bile  begins  to  increase  in  quantity;  but  these 
observers  state  that  it  is  at  its  maximum  from  the  twelfth 
to  the  fifteenth  hour.  This,  however,  is  not  material  to 
the  question  now  under  consideration.  I  wished  to  estab- 
lish the  fact  that  the  quantity  of  bile  secreted  varied  con- 
siderably during  the  various  stages  of  the  digestive  act;  a 
character  which  approximates  it  to  other  secretions.  The 
flow'  of  the  bile  is  not  intermittent,  because  it  contains  a 
substance  which  is  excrementitious;  but  it  is  remittent, 
having  a  definite  relation  to  the  digestive  act,  because  it 
■contains  substances  which  are  recrementitious  and  are  in 
some  way  connected  with  the  process  of  digestion. 

The  continuous  though  remittent  flow  of  the  bile  al- 
lies it  with  the  excretions.  There  is  no  time,  in  health, 
when  the  bile  is  not  separated  from  the  blood.  In  animals 
that  go  through  the  process  of  hibernation,  the  bile  con- 
tinues to  be  secreted,  though  no  food  is  taken  into  the 
alimentary  canal.  Nutrition,  though  much  diminished  in 
activity,  goes  on  during  this  state,  and  the  urea  and  cho- 
lesterin  must  be  separated  from  the  blood.  The  formation 
of  the  bile  and  urine,  therefore,  is  not  interrupted.  Bile  is 
secreted  also  in  the  foetus,  before  any  nourishment  is  taken 
into  the  alimentary  canal,  when  none  of  the  other  digestive 
fluids  are  formed.  This  character  it  has  in  common  with 
the  urine,  and  this  places  it  among  the  excretions. 

The  elements  of  secretion  never  accumulate  in  the  sys- 
tem when  the  secretion  is  interfered  with;  while  the  ele- 
ments of  excretion  do  accumulate  in  the  blood  in  such 
cases  and  produce  certain  toxic  effects.  Experimenters 
have  often  analyzed  the  blood  for  the  biliary  salts  in  cases 
of  serious  disease  of  the  liver,  marked  by  symptoms  of  bile- 
poisoning,  regarding  these  as  the  only  important  elements 


204  NEW    FUNCTION   OF  THE    LIVER 

of  the  bile;  but  they  have  never  been  detected.  I  have 
made  no  observations  on  this  point,  for  the  fact  that  the 
glycocholate  and  taurocholate  of  soda  do  not  accumulate 
in  the  blood  in  diseases  of  the  liver  has  long  been  set- 
tled. This  stamps  these  substances  as  products  of  secre- 
tion; l)ut  we  shall  see  when  some  of  the  pathological  con- 
ditions of  the  cholesterin  are  taken  up,  that  this  substance 
does  accumulate  in  the  blood  when  the  functions  of  the 
liver  are  seriously  interfered  with,  which  marks  it  as  a 
product  of  excretion. 

It  seems  to  me  that  enough  has  been  said  in  regard 
to  the  function  of  the  bile  to  convince  the  reader  that 
this  complex  fluid  has  two  important  ingredients  which 
have  two  separate  functions. 

First. — It  contains  the  glycocholate  and  taurocholate 
of  soda,  which  are  not  found  in  the  blood,  are  manufac- 
tured in  the  liver,  are  discharged  mainly  at  a  certain  stage 
of  the  digestive  process,  are  destined  to  assist  in  some  of 
the  nutritive  processes,  are  not  discharged  from  the  body 
and,  in  fine,  are  products  of  secretion. 

Second. — It  contains  cholesterin,  which  is  found  in  the 
blood,  is  merely  separated  from  it  by  the  liver  and  not 
manufactured  in  this  organ,  is  not  destined  to  assist  in  any 
of  the  nutritive  processes  but  is  merely  separated  to  be 
discharged  from  the  body,  and  is  a  product  of  excretion. 

These  two  propositions,  especially  the  second,  being 
established,  it  becomes  necessary  now  to  follow  out  choles- 
terin after  it  has  been  discharged  from  the  liver  into  the 
small  intestine.  If  it  is  discharged  from  the  body  it  must 
be  by  the  rectum ;  and  to  complete  the  history  of  cholesterin 
it  becomes  necessary  to  study  the  feces. 

Feces. — It  is  not  my  object  to  consider  all  the  effete 
matters  which  go  to  make  up  the  feces,  although  it  must 
be  acknowledged  that  information  on  this  subject  is  very 
limited.  Following  cholesterin  in  its  passage  down  the 
alimentary  canal  has  opened  a  new  subject  for  investiga- 
tion, to  which  it  will  be  impossible  to  do  entire  justice 
in  this  paper.  There  is  a  field  for  a  long  series  of  investiga- 
tions into  this  part  of  our  subject,  which  I  hope  to  be  able 
to  cultivate  to  some  extent  in  the  future  and  to  add  some- 
thing to  the  history  of  the  substance  I  have  been  con- 
sidering.     At   present   I   shall   endeavor  only   to  demon- 


NEW   FUNCTION   OF  THE    LIVER  205 

strate  the  fact  that  cholesterin,  in  a  modified  form,  is  dis- 
charged with  the  feces,  and  not  attempt  to  treat  of  the 
conditions  which  modify  the  excretion  of  this  snl^stance 
(upon  which  as  yet  I  have  no  data),  which  are  of  great 
importance  to  the  practical  physician. 

It  is  stated  by  some  of  the  most  rehable  authors  on 
physiology  and  physiological  chemistry  that  cholesterin  is 
found  in  the  fecal  matters.  Robin  and  Verdeil  say,  "  Ce 
principe  immediat  se  trouve  a  I'etat  normal  dans  le  sang, 
la  bile,  le  foie,  le  cerveau,  les  nerfs,  le  crystallin  et  les  ma- 
tieres  fecales."  Many  other  authors  refer  to  it  as  found 
in  the  feces,  and  it  was  with  that  belief,  that,  in  the  ex- 
periments which  form  the  basis  of  this  article,  I  deferred 
my  analyses  of  the  feces  till  I  had  completed  the  observa- 
tions on  the  blood,  and  then  analyzed  them,  satisfied  that 
I  should  find  cholesterin,  with  the  view  to  determine  the 
variations,  etc.,  in  its  quantity.  When,  after  a  careful  and 
prolonged  examination  of  many  specimens  of  feces,  I  was 
unable  to  extract  any  cholesterin,  I  endeavored  to  ascer- 
tain what  observer  had  established  its  presence.  Though  it 
is  mentioned  by  so  many  as  present  in  fecal  matter,  I  could 
iind  no  mention  of  any  one  who  had  established  this  point; 
and  in  some  of  the  analyses  of  Simon.  I  found  that  he  had 
noted  its  absence  in  certain  specimens  of  feces.  I  found 
also  that  Marcet,  who  published  some  elaborate  analyses 
of  the  feces  in  the  "  Philosophical  Transactions,"  in  1854 
and  1857,  noted  the  absence  of  cholesterin  in  the  normal 
feces  of  the  human  subject.  It  has  already  been  seen  how 
conclusively  the  experiments  on  the  blood  from  various 
parts  of  the  system  point  to  the  excrementitious  character 
of  cholesterin,  showing,  even,  in  what  part  of  the  sys- 
tem it  is  found  and  where  it  is  eliminated;  but  it  is  un- 
doubtedly one  of  the  most  important  characters  of  an  ex- 
cretion that  it  should  be  discharged  from  the  body,  and 
I  was  unable  for  a  time  to  convince  myself  that  it  was  dis- 
charged. After  evaporating  the  feces  to  dryness,  pulver- 
izing, extracting  thoroughly  with  ether,  decolorizing  with 
animal  charcoal,  evaporating  the  ether  and  extracting  the 
residue  with  boihng  alcohol,  I  allowed  the  alcohol  to  evap- 
orate, added  a  solution  of  caustic  potash,  and  kept  the 
mixture  at  a  temperature  near  the  boiling  point  for  three 
and   a   quarter   hours.      The    potash   was    then    carefully 


2o6  NEW    FUNCTION   OF  THE    LIVER 

washed  away  on  a  filter,  the  residue  rechssolved  in  ether 
and  extracted  with  hot  alcohol  as  before,  and  the  alcoholic- 
extract  set  aside  to  evaporate.  A  number  of  days  passed 
without  any  sign  of  crystallization.  The  residue  was,  of 
course,  non-saponifiable;  but  it  differed  from  cholesterin 
by  being  melted  at  a  much  lower  temperature,  though  it 
presented  the  red  color  with  sulphuric  acid  which  is  said 
to  be  characteristic  of  the  latter  substance.  It  w^as  exam- 
ined carefully  with  the  microscope  daily;  and  after  five 
or  six  days,  to  my  great  satisfaction,  crystals  began  to 
appear;  but  they  were  at  first  so  indistinct  that  their  form 
could  not  be  clearly  made  out.  These  crystals,  however, 
increased  in  size  and  number,  and  in  a  short  time  pre- 
sented the  characteristics  of  serolin.  In  about  ten  days  the 
whole  mass  had  crystallized,  making  one  of  the  most  su- 
perb exhibitions  of  crystals  that  could  be  imagined.  Sero- 
lin crystallizes  in  the  form  of  delicate  transparent  needles, 
which  have  a  beauty  under  the  microscope  which  could  be 
but  poorly  imitated  by  the  most  delicate  steel  plate  en- 
graving. This  substance,  from  its  being  found  in  such  large 
quantity  in  the  feces,  I  have  spoken  of  as  stercorin. 

Before  taking  up  the  changes  which  cholesterin  under- 
goes in  its  passage  down  the  alimentary  canal,  I  shall  say 
a  few  words  in  regard  to  stercorin. 

STERCORIN 

Stercorin  has  already  been  referred  to  and  delineated 
in  the  analyses  of  various  specimens  of  blood  for  choles- 
terin. It  was  observed  by  Boudet  and  described  by  him 
under  the  name  of  seroline,  in  an  article  published  in  the 
"  Annales  de  chimie  et  de  physique,"  in  1833,  as  a  prin- 
ciple found  in  the  serum  of  the  blood.  Up  to  the  present 
time,  this  is  the  only  situation  in  w^hich  it  has  been  found, 
and  here  in  such  an  excessively  minute  quantity  that 
enough  has  never  been  obtained  for  ultimate  chemical 
analysis.  In  regard  to  its  function  nothing  whatever 
has  been  known.  Robin  thus  speaks  of  it:  "  On  ne  sait 
pas  comment  se  forme  la  seroline,  ni  quel  est  son  role 
physiologique."  * 

*  Robin  and  Verdeil,   "  Chimie  anatomique  et  physiologique,"  tome  iii.^ 
p.  66. 


NEW   FUNCTION   OF   THE    LIVER  207 

Chemical  Characters. — This  substance,  like  choles- 
terin,  is  a  non-saponifiable  fat.  It  has  never  been  obtained 
in  sufficient  quantity  for  ultimate  chemical  analysis;  but  as 
in  its  decomposition  it  disengages  a  little  ammonia,  it  is 
supposed  by  Verdeil  and  Marcet  to  contain  nitrogen.* 
The  evidences  of  this  ingredient  are  very  slight,  and  its 
existence  is  doubtful.  It  is  neutral,  inodorous,  insoluble 
in  water,  soluble  in  ether,  very  soluble  in  hot  alcohol  but 
almost  insoluble  in  cold.  It  is  not  attacked  by  the  caustic 
alkalies,  even  after  prolonged  boiling-.  When  treated  with 
strong  sulphuric  acid  it  strikes  a  red  color  similar  to 
that  produced  by  sulphuric  acid  and  cholesterin.  Ac- 
cording to  Lehmann  it  melts  at  96.8°  Fahr.,  and  on  the 
application  of  strong  heat  may  be  distilled  without  change. 
Boudet  extracted  it  from  the  serum  of  the  blood  by  evap- 
orating, boiling  the  residue  with  water  and  evaporating 
again,  taking  up  the  residue  with  boiling  alcohol,  which 
deposited  the  crystals  on  cooling. 

Form  of  its  Crystals. — Boudet  describes  the  crystals 
thus  obtained  as  filaments,  with  varicosities  here  and  there 
which  gave  them  a  beaded  appearance.  Lecanu  also  ob- 
served this  peculiarity.  In  the  atlas  of  Robin  and  Verdeil's 
"  Chimie  anatomique  "  there  is  a  beautiful  representation 
of  the  crystals  of  serolin  from  the  blood.  These  observ- 
ers have  not  noticed  the  beaded  appearance  mentioned 
by  Boudet,  but  represent  the  crystals  in  the  form  of  deli- 
cate transparent  needles,  of  variable  size,  some  very  small 
and  others  quite  wide,  terminating  in  fine  pointed  extrem- 
ities, which  in  some  of  the  wider  crystals  is  bifurcated 
or  even  trifurcated,  with  the  edges  of  the  larger  crystals 
frequently  split,  as  it  were,  into  delicate  filaments.  The 
smaller  crystals  frequently  arrange  themselves  in  a  fan- 
shape.  Robin  and  Verdeil  attribute  the  beaded  appear- 
ance mentioned  by  Boudet  and  Lecanu  to  the  presence 
of  little  globules  of  fatty  matter  mixed  with  the  crystals. 
This  seems  probable,  for  it  will  be  seen  in  examining  the 
process  of  extraction  employed  by  Boudet,  that  he  prob- 
ably did  not  succeed  in  obtaining  it  in  a  pure  form.  The 
appearance  of  these  crystals  has  already  been  given  in  some 
of  the  diagrams  of  cholesterin,  especially  in  Figs.  2,  6,  7, 

*  "  Cours  de  physiologic  fait  a  la  Faculte  de  Medecine  de  Paris."     Par  P. 
Berard,  Professeur  de  Physiologic,  etc.    Paris,  1851,  tome  iii.,  p.  118. 


2o8  NEW    FUNCTION   OF  THE    LIVER 

and  9.  I  have  been  able  to  follow  the  process  of  crystal- 
lization in  the  specimens  extracted  from  the  feces  from 
its  beginning,  and  have  found  that  the  splitting  of  the 
ends  and  edges  of  the  crystals  did  not  take  place  at  first. 
The  needles  which  were  first  formed  had  regular  borders 
and  single  pointed  extremities;  but  after  a  few  days  they 
split  up  in  the  manner  described  and  figured  by  Robin  and 
Verdeil.     (See  Figs.  14  and  15.) 

Situations. — Up  to  this  time,  serolin  (or  stercorin) 
has  been  found  only  in  the  serum  of  the  blood,  and  there 
in  but  very  small  quantity,  the  proportion  being,  according 
to  the  analyses  of  Becquerel  and  Rodier,  0.020  to  0.025 
of  a  part  per  1,000  parts  of  blood.  They  have  seen  it  mount 
up  to  0.060  parts,  and  descend  to  a  quantity  almost  in- 
appreciable.* 

Process  of  Extraction. — In  the  first  observations  I 
made  on  the  blood  this  substance  was  observed  before 
cholesterin.  In  these  observations  the  blood  was  dried, 
pulverized,  extracted  with  ether,  the  ether  evaporated,  the 
residue  extracted  with  boiling  alcohol  and  then  a  solution 
of  caustic  potash  added  which  remained  on  the  specimens 
for  a  number  of  days.  In  all  the  subsequent  analyses  of 
the  blood  cholesterin  was  extracted  perfectly  pure,  and  no 
stercorin  whatever  was  observed.  The  following  was  the 
difference  in  the  modes  of  analysis.  In  the  latter  case 
the  solution  of  potash  was  not  allowed  to  remain  on  the 
specimens  more  than  an  hour  or  two;  but  was  washed 
aw^ay,  and  the  residue  which  was  left  on  the  filter  was  redis- 
solved  in  ether.  The  failure  to  detect  the  stercorin  in  all 
the  later  observations  on  the  blood,  which  are  twenty-four 
in  number,  inclines  me  to  the  opinion  that  it  does  not  pri- 
marily exist  in  this  fluid;  and  that  when  it  has  appeared 
in  the  extract  it  has  been  due  to  a  transformation  of  a 
portion  of  the  cholesterin.  This  view  seems  the  more  prob- 
able as  I  have  definitely  ascertained  by  observations  on 
the  feces,  which  will  be  detailed  farther  on,  that  cholesterin 
is  capable  of  being  changed  into  stercorin,  and  that  this 
change  actually  takes  place  before  it  is  discharged  from 
the  body.  In  my  observations  on  the  blood  no  attempt 
was  made  to  get  rid  of  this  substance;  and  though  it  is 

*  "  Traite  de  chimie  pathologique  appliqude  k  la  medecine  pratique."     Par 
MM.  Alf.  Becquerel  and  A.  Rodier.     Paris,  1854,  p.  62. 


NEW    FUNCTION   OF  THE    LIVER  209 

soluble  in  the  menstrua  which  were  used  to  extract  cho- 
lesterin  and  is  not  destroyed  by  any  of  the  means  that 
were  employed  to  purify  the  cholesterin,  it  never  appeared 
in  the  extract.  In  these  experiments  the  study  of  ster- 
corin  in  the  blood  has  not  been  attempted;  and  though  it 
is  not  possible  to  state  at  present  how  the  cholesterin  was 
transformed  in  the  first  observations,  it  seems  most  rational 
to  suppose,  in  endeavoring  to  explain  its  absence  in  the 
twenty-four  succeeding  specimens  of  blood  which  were  ex- 
amined, that  such  a  change  had  taken  place. 

I  am  inclined  to  the  opinion,  then,  though  I  can  not 
state  it  positively,  that  the  substance  under  consideration 
•does  not  exist  in  the  blood  as  a  proximate  principle,  but 
is  formed  from  cholesterin,  in  some  unexplained  way,  by 
the  processes  which  have  been  used  for  its  extraction.* 
This  transformation  does  not  take  place  during  the  ex- 
traction of  this  substance  from  the  feces,  because  I  have 
in  but  a  single  instance  been  able  to  extract  cholesterin  by 
the  processes  which  are  successful  in  obtaining  it  in  other 
situations  in  which  it  exists,  including  meconium. 

Stercorin  may  be  extracted  from  the  feces  in  the  fol- 
lowing way:  The  feces  are  evaporated  to  dryness,  pulver- 
ized and  treated  with  ether,  which  should  be  allowed  to 
remain  for  twelve  to  twenty-four  hours,  protected  from 
evaporation.  The  ether  is  then  separated  and  decolorized 
by  filtration  through  animal  charcoal,  fresh  ether  being 
added  till  the  original  quantity  has  passed  through.  It  is 
impossible  to  decolorize  the  solution  entirely,  but  it  should 
be  made  to  pass  through  of  a  very  pale  amber  tinge  and 
perfectly  clear.  The  ether  is  then  evaporated  and  the  resi- 
due extracted  with  boiling  alcohol.  The  alcohol  is  then 
evaporated  and  the  residue  treated  with  a  solution  of  caus- 
tic potash,  at  a  temperature  a  little  below  the  boiling  point, 
for  one  or  two  hours.  This  dissolves  all  the  saponifiable 
fats,  and  the  solution  is  then  largely  diluted  with  water, 
thrown  on  a  filter  and  washed  till  the  fluid  which  passes 
through  it  is  perfectly  clear  and  neutral.  The  filter  is  then 
dried  at  a  moderate  temperature  and  the  residue  washed 

*  In  the  absence  of  an  ultimate  analysis  of  this  substance,  it  is  impossible 
to  enter  into  any  chemical  speculations  in  regard  to  the  change  from  choles- 
terin, as  in  the  instance  of  creatin  and  creatinin  or  urea  and  carbonate  of  am- 
monia. 

14 


2IO  NEW    FUNCTION    OF  THE    LIVER 

out  with  ether,  which  is  evaporated,  extracted  with  boiling 
alcohol  and  evaporated  again.  The  residue  is  composed 
of  pure  stercorin.*  The  extract  thus  obtained  is  a  clear, 
slightly  amber,  oily  substance,  of  about  the  consistence  of 
the  ordinary  Canada  balsam  used  in  microscopic  prepara- 
tions, and  in  four  or  five  days  begins  to  show  the  charac- 
teristic crystals.  These  are  at  first  few  in  number;  but  soon 
the  entire  mass  assumes  a  crystalline  form.  In  a  specimen 
which  I  extracted  from  the  feces  I  have  10.417  grains, 
consisting,  apparently,  of  nothing  but  crystals.  If  the  ex- 
tract *is  evaporated  in  a  very  thin  watch-glass  it  may  be 
examined  with  the  microscope  daily  and  the  process  of 
the  formation  of  the  crystals  observed.  These  crystals, 
after  they  are  fully  formed,  may  be  examined  satisfactorily 
with  a  half  or  quarter-inch  objective. 

History  of  Serolin. — Very  little  is  to  be  said  in 
regard  to  the  history  of  this  substance.  Boudet  first  de- 
scribed it  in  i833.f  Lecanu  confirmed  these  observations 
in  1837.:!:  Since  then  it  has  been  studied  by  Becquerel  and 
Rodier,"  Chatin  and  Sandras,||  W.  Marcet  and  Verdeil."^ 
Gobley  states,  in  an  article  published  in  the  "  Journal  de 
chimie  medicale,"  that  the  substance  described  by  Boudet 
is  not  an  immediate  principle  but  a  mixture  of  several  sub- 
stances, confounding  it,  how^ever,  with  cholesterin.O  Ro- 
bin and  Verdeil  adopt  this  view,  but  consider  it  entirely 
different  from  cholesterin.l 

This  substance,  existing,  as  it  does,  in  large  quantities. 
in  the  fecal  matter,  must  take  its  place  among  the  im- 
portant excrementitious  matters  discharged  from  the  or- 
ganism, not  second  in  importance,  even,  to  urea.  It  is 
a  curious  fact  that  while  urea  was  known  as  an  ingredi- 
ent of  the  urine   long  before  it  could   be  demonstrated 

*  As  this  substance  is  said  to  be  volatilized  at  a  high  temperature,  it  is  im- 
portant to  avoid  as  much  as  possible  the  application  of  heat.  Large  quantities 
of  it  are  extracted  from  the  feces  after  evaporation  over  an  ordinary  water  bath, 
but  it  might  be  better  to  evaporate  the  excrements  at  a  lower  temperature. 

\  Boudet.     Loc.  cit. 

X  Lecanu.      "  Etudes  chim.  sur  le  sang  humain,  these."     Paris,  1837,  p.  55. 

*  Becquerel  and  Rodier.  "  Recherches  relatives  a  la  comp.  du  sang." 
("  Comptes  Rendus."     Paris,  144,  tome  xix.,  p.  1084.) 

II  Chatin  et  Sandras.     "  Gaz.  des  hopit.,"  1849,  p.  289. 
'^  Berard.     Loc.  cit. 

0  Gobley.      "Sur   les   matieres   grasses   du    sang."      ("Journal    de    chimie 
medicale,"  185 1.     Paris,  p.  577.) 
%  Robin  et  Verdeil.     Loc.  cit. 


NEW   FUNCTION   OF   THE    LIVER  211 

in  the  blood,  taking  its  name  from  that  fluid,  stercorin,  an 
excrement  of  great  importance,  was  discovered  in  the  blood 
and  never  till  now  has  been  recognized  as  an  excrement 
and  an  ingredient  of  the  feces,  taking  a  name  from  the 
serum  of  the  blood,  which  does  not  indicate  at  all  its  ex- 
crementitious  properties  or  the  situation  in  which  it  is 
found  in  g^reatest  abundance.  As  seroHn  has  been  here- 
tofore  a  substance  of  very  little  prominence,  and  as  it 
probably  does  not  exist  normally  in  the  serum  of  the  blood, 
and  if  at  all,  in  insignificant  quantity,  the  appellation  seems 
a  misnomer.  It  should  be  known  by  a  name  which  will 
indicate  its  excrementitious  properties  and  the  channel  by 
which  it  is  evacuated;  and  I  have  adopted  the  name  Ster- 
corin *  as  more  appropriate  and  more  suggestive  of  its 
properties,  as  it  is  undoubtedly  the  most  important  ex- 
crement discharged  by  the  anus. 

The  questions  which  now  arise  in  regard  to  this  sub- 
stance open  a  field  of  inquiry  too  extensive,  by  far,  to  be 
thoroughly  investigated  in  the  time  that  could  be  devoted 
to  this  subject,  or  to  be  discussed  within  the  limits  of  this 
paper.  It  would  be  desirable  to  know  the  full  history 
of  this  product,  the  quantity  discharged  in  twenty-four 
hours,  variations  that  may  take  place  with  season,  age,  sex, 
diet,  digestion,  etc.,  and  especially  the  modifications  which 
occur  in  its  discharge  in  connection  with  diseased  condi- 
tions. These  points  are  of  great  importance;  but  they 
require  a  long  and  laborious  series  of  investigations  for 
their  elucidation.  What  has  been  done  in  a  measure  for 
urea  must  be  done  for  stercorin,  before  arriving  at  a 
precise  idea  of  its  relations  to  disease.  For  this  pur- 
pose a  large  number  of  quantitative  analyses  of  healthy 
feces  must  be  made  and  compared  with  similar  analyses 
in  different  diseases.  At  present  I  have  instituted  only  a 
sufficient  number  of  examinations  to  substantiate  the 
statements  I  have  made  in  regard  to  the  formation  and 
discharge  of  this  substance,  and  have  added  a  few  exam- 
inations of  feces  in  disease  which  bear  upon  the  same 
points.  I  hope  at  some  future  time  to  go  more  fully  into 
the  study  of  the  feces  and  to  contribute  something  toward 
the  elucidation  of  some  of  the  questions  which  naturally 

*  From  Stercus,  6ris,  dung. 


212  NEW    FUNCTION   OF   THE    LIVER 

arise.     In  the  mean  time  I  present  the  following  observa- 
tions on  stercorin  as  it  appears  in  the  feces: 

Experiment  IX. — Seven  and  a  half  ounces  of  feces,  perfectly- 
normal  in  appearance  and  being  the  entire  quantity  passed  in  the 
morning  at  the  regular  time  for  an  evacuation,  were  taken  from 
a  healthy  male,  twenty-six  years  of  age.  After  being  evaporated 
and  finely  pulverized  in  an  agate  mortar,  the  residue  weighed  2  oz. 
57.313  grains.  A  small  quantity  was  then  extracted  with  alcohol, 
the  solution  being  of  a  yellow  color,  and  about  six  times  its  vol- 
ume of  ether  added.  The  ether  was  filtered  after  standing  for 
fifteen  minutes,  the  filter  washed  with  distilled  water,  and  the  solu- 
tion tested  with  Pettenkofer's  test  for  the  biliary  salts.  None  of 
these  salts  were  present. 

A  watery  solution  was  then  made  of  another  portion,  which 
was  filtered  and  tested  with  nitric  acid,  but  failed  to  show  the  reac- 
tions of  the  coloring  matter  of  the  bile. 

The  dry  residue  was  then  treated  with  five  fluidounces  of  ether 
for  twenty  hours,  when  it  was  filtered  through  animal  charcoal, 
fresh  ether  being  added  till  the  fluid  which  passed  through  made 
five  ounces.  It  came  through  perfectly  clear  and  of  a  very  light 
golden  tinge.  It  was  then  evaporated,  leaving  a  golden  yellow  fat 
with  a  number  of  whitish  resinous  masses.  It  was  then  extracted 
with  ojss  of  boiling  alcohol,  which  removed  everything  but  a  small 
quantity  of  bright  yellow  oil,  and  filtered  while  hot.  It  became 
turbid  on  cooling  and  was  set  aside  to  evaporate.  Both  the  ethereal 
and  alcoholic  extracts  had  a  very  offensive  rancid  odor.  The 
residue,  after  the  evaporation  of  the  alcohol,  consisted  of  a  con- 
siderable quantity  of  fat  of  a  yellowish  color  and  of  a  consistence 
like  thick  turpentine.  It  was  then  treated  with  a  solution  of  caustic 
potash,  kept  near  212°  for  about  thirty  minutes  and  allowed  to 
stand  for  twenty  hours.  At  the  end  of  that  time  a  large  quantity 
of  fat  floated  on  the  top  of  the  fluid  not  at  all  affected  by  the  al- 
kali. It  was  then  largely  diluted  with  distilled  water  filtered  and 
washed,  the  filter  dried,  and  the  residue  redissolved  in  ether.  This 
ethereal  solution  was  evaporated  and  the  residue  extracted  with 
boiling  alcohol  as  before.  After  the  alcohol  had  evaporated,  a 
small  quantity  was  treated  with  sulphuric  acid  which  produced  a 
peculiar  red  color  similar  to  that  produced  when  the  acid  was 
added  to  a  specimen  of  cholesterin,  extracted  from  the  blood  and 
used  for  purposes  of  comparison. 

Five  days  after,  the  specimen  was  examined  with  a  T*oth  inch 
objective  and  presented  some  crystals  which  looked  like  serolin ; 
but  it  was  impossible,  on  account  of  the  thickness  of  the  glass  cap- 
sule, to  apply  a  sufficiently  high  power  to  make  this  certain.  Some 
long,  pale,  radiating  crystals  were  observed,  composition  unknown, 
"but  they  were  not  the  crystals  of  excretin  described  by  Marcet.* 

*  Marcet,  in  two  papers  published  in  the  "  Philosophical  Transactions"  for 
1S54  and  1857,  describes  a  new  proximate  principle  in  the  feces  which  he  calls 
Excretin.      This  he  obtains  in  the  following  way  :    He  first  treats  the  feces 


NEW    FUNCTION    OF  THE    LIVER  213 

The  specimen  was  treated  again  with  a  solution  of  caustic  potash 
and  kept  at  nearly  the  boiling  point  of  water  for  three  and  a  quarter 
hours,  most  of  the  fat  floating  on  the  top  of  the  fluid  in  white  flakes 
and  yellow  drops,  but  a  considerable  quantity  undergoing  saponi- 
fication, as  evidenced  by  the  color  of  the  potash  solution.  The 
potash  was  then  removed  by  filtration,  the  residue  dissolved  in 
ether  and  extracted  with  boiling  alcohol  as  before. 

Four  days  after  the  evaporation  of  the  alcohol,  a  large  number 
of  the  characteristic  crystals  were  formed.  These  did  not  have  the 
split  extremities  and  edges  noted  by  Robin,  but  terminated  in  a 
single  point  and  had  regular  borders.  The  crystals  are  represented 
in  Fig.  14. 

In  a  few  days  the  entire  mass  had  assumed  a  crystalline  form, 
and  the  crystals  then  presented  split  extremities  and  borders  such 
as  are  mentioned  by  Robin.     (See  Fig.  15.) 

The  quantity  of  stercorin  was  10.417  grains. 

Experiment  X. — Another  analysis  was  made  of  the  feces  from 
the  same  individual.  During  the  experiment  a  large  quantity  was 
unfortunately  lost,  and  the  examination,  therefore,  was  not  quan- 
titative.    The  presence  of  stercorin  was  established. 

Experiment  XI. — The  feces  of  the  dog  from  which  blood  of 
the  carotid  and  internal  jugular  on  one  side  had  been  taken  fifteen 
days  before,  the  animal  having  entirely  recovered,  were  exam- 
ined. The  analysis  was  not  quantitative.  The  feces  were  treated 
in  the  way  already  described  and  the  presence  of  stercorin  de- 
termined. 

Experiment  XII. — A  specimen  of  feces  voided  by  a  healthy 
dog,  fasting,  was  examined  in  the  usual  way  for  stercorin.  After 
the  final  extract  had  evaporated,  it  was  examined  microscopically 
and  found  to  contain,  in  addition  to  stercorin,  a  considerable  quan- 
tity of  cholesterin,  crystallized  in  beautiful  tablets.     This  is  the 

with  boiling  alcohol  till  nothing  more  can  be  extracted.  A  sediment  deposits 
from  the  alcohol  on  cooling.  The  alcoholic  solution  is  acid.  Milk  of  lime  is 
added  to  the  solution,  which  gives  a  yellowish-brown  precipitate,  leaving  a 
clear  straw-colored  fluid.  The  precipitate  is  then  collected  on  a  filter,  dried, 
afterwards  agitated  with  ether  and  filtered,  forming  a  clear  yellow  solution.  In 
one  to  three  days,  beautiful  silky  crystals  collect  in  masses,  or  tufts,  adhering 
to  the  sides  of  the  vessel,  throwing  out  ramifications  in  every  direction.  These, 
viewed  under  the  microscope,  are  in  the  form  of  acicular,  four-sided  prisms, 
and  this  substance  is  called  by  Dr.  Marcet,  excretin,  and  is  found  nowhere 
but  in  the  feces.  It  is  soluble  in  ether  and  hot  alcohol,  sparingly  so  in  cold 
alcohol,  and  insoluble  in  hot  or  cold  water.  It  does  not  crystallize  from  an 
alcoholic  solution  on  cooling  but  crystallizes  from  ether.  When  suspended  in 
boiling  water  it  fuses  into  resinous  masses,  and  floats  on  the  top.  Its  fusing 
point  is  203°  to  205°  Fahr.  It  may  be  boiled  for  hours  with  potash  without 
undergoing  saponification. 

In  the  article  published  in  1857,  Dr.  Marcet  gives  the  composition  of  the 
excretin  Cts  Hvs  O2  S,. 

There  is  no  similarity  between  the  form  of  the  substance  described  by 
Marcet  and  stercorin.  Its  high  fusing  point,  203°  to  205°  Fahr.,  and  its 
crystallization  from  an  ethereal  solution,  also  serve  to  distinguish  it  from 
stercorin,  which  fuses  at  96.8°  Fahr.  and  does  not  crystallize  from  an  ethereal 
solution. 


214  NEW    FUNCTION   OF   THE    LIVER 

only  examination  of  feces  in  which  I  have  found  cholesterin.     The 
proportion  of  stercorin  and  cholesterin  was  as  follows : 

Quantity  of  feces ' 37-5 ' 3  grains. 

Stercorin  with  a  little  cholesterin 0.216      " 

These  examinations  of  the  feces  in  health  show  that 
they  invariably  contain  a  non-saponihable  substance  known 
under  the  name  of  serolin,  but  which  I  have  called  ster- 
corin. In  but  one  of  these  analyses,  the  last,  did  I  find 
any  cholesterin,  though  the  first  were  originally  undertaken 
with  a  view  to  the  extraction  of  this  substance. 

Stercorin  has  never  before  been  detected  in  the  feces; 
and,  so  far  as  my  knowledge  of  its  physiological  properties 
is  concerned,  it  may  be  considered  a  new  substance,  the 
discovery  of  which,  in  this  situation,  marks  it  as  one  of  the 
most  important  of  the  products  of  destructive  assimilation. 
The  next  question  which  arises,  then,  is  in  regard  to  its 
origin. 

Origin  of  Stercorin. — In  the  study  of  the  chemical 
properties  of  this  substance,  it  has  been  seen  that  it  is  one 
of  the  non-saponifiable  fats,  having  many  characters  in 
common  with  cholesterin.  It  has  been  described,  uiider 
the  name  of  serolin,  as  found  in  the  blood  in  minute  quan- 
tity, but  it  does  not  exist  in  any  of  the  fluids  which  are 
poiu-ed  into  the  alimentary  canal.  Cholesterin,  however, 
which  it  so  closely  resembles,  is  one  of  the  constituents 
of  the  bile.  The  fact  that  cholesterin  is  discharged  into 
the  small  intestine  and  is  not  usually  found  in  the  evacu- 
ations, while  stercorin  is  abundant,  would  at  once  point 
to  a  possible  connection  between  these  two  substances.  In 
most  cases,  in  health,  cholesterin  disappears  and  stercorin 
is  found;  but  in  some  rare  instances,  as  in  the  single  exam- 
ination of  dogs'  feces  (Experiment  XII.),  the  two  sub- 
stances coexist  in  the  evacuations,  stercorin,  in  the  exam- 
ple just  mentioned,  in  much  the  greater  quantity.  The 
question  then  arises:  Is  cholesterin  capable  of  being  con- 
verted into  stercorin,  and  does  the  latter  substance  orig- 
inate from  a  transformation  of  the  cholesterin  of  the  bile? 
Before  treating  of  this  subject  experimentally,  I  shall  ex- 
amine the  facts  already  ascertained  bearing  on  this  point. 
No  examinations  of  the  feces  have  ever  been  made  for  ster- 
corin; but  under  certain  conditions  cholesterin  has  been 
found  discharged  by  the  anus  without  alteration. 


NEW    FUNCTION   OF  THE    LIVER  215 

Cholesterin  has  already  been  found  in  the  meconium, 
in  the  feces  of  hibernating  animals  and  occasionally  in 
ordinary  feces. 

Meconium. — Cholesterin  exists  in  meconium  in  con- 
siderable quantity,  where  it  may  be  seen  in  tablets  in  a 
simple  microscopic  examination,  and  from  which  it  may 
be  extracted  in  quantity  and  with  great  facility.  Sterco- 
rin  (or  serolin)  has  never  been  mentioned  as  existing  in 
this  situation.  In  the  single  examination  I  have  made  of 
the  meconium,  I  found  an  abundance  of  cholesterin,  6.245 
parts  per  1,000,  but  no  stercorin.  There  is  no  difficulty 
in  explaining  the  origin  of  the  cholesterin  in  meconium. 
Long  before  any  food  is  taken  into  the  alimentary  canal 
and  before  the  exclusively  digestive  fluids  are  formed,  the 
bile  is  secreted  and  discharged.  It  accumulates  in  the  in- 
testine, with  other  matters  constituting  the  meconium,  and 
is  finally  evacuated  soon  after  birth.  Hence  cholesterin 
exists  in  large  abundance;  but  when  the  digestive  fluids 
are  secreted  and  food  is  received  into  the  alimentary  canal, 
the  cholesterin  is  lost  and  stercorin  makes  its  appearance. 

Feces  of  Hibernating  Animals. — As  the  excretory 
function  of  the  liver  begins  before  food  is  taken  into  the 
alimentary  canal,  so  it  goes  on  during  the  state  of  hiberna- 
tion, when  the  animal  takes  no  food  for  weeks  or  even 
months.  Under  these  conditions,  cholesterin  is  found  un- 
changed in  the  feces;  but  it  disappears  when  the  animal 
arouses  and  the  digestive  organs  resume  their  functions. 

Normal  Feces. — In  the  normal  feces  cholesterin  is 
generally  absent;  but  in  Experiment  XII.,  it  was  found 
in  small  quantity,  mixed  with  stercorin.  This  animal  had 
been  certainly  twenty-four  hours,  and  probably  forty-eight 
hours  without  food.  The  feces  were  of  normal  color  and 
consistence. 

These  facts  seem  to  show  that  before  digestion  begins, 
as  in  the  foetus,  and  when  it  is  suspended,  as  in  hibernating 
animals  and  in  Experiment  XII.,  cholesterin  passes 
through  the  alimentary  canal  unchanged;  but  so  soon  as 
digestion  begins,  cholesterin  is  lost  in  the  feces  and  its 
place  is  supplied  by  stercorin.  It  seems  almost  certain, 
then,  that  in  its  passage  down  the  alimentary  canal,  the 
cholesterin  of  the  bile  is  acted  upon  by  some  of  the  di- 
gestive fluids  and  changed  into  stercorin.     This  change 


2i6  NEW   FUNCTION  OF  THE   LIVER 

seems  to  be  incident  to  the  digestive  act;  for  before  diges- 
tion begins  and  when  it  is  suspended,  cholesterin  passes 
through  unchanged.  A  conclusive  observation  would  be 
to  cut  off  the  bile  from  the  intestines,  and  consequently 
the  cholesterin,  and  note  the  effect  upon  the  production 
of  stercorin.  In  a  case  of  jaundice  from  duodenitis  (which 
w'ill  be  more  minutely  detailed  in  the  section  on  the  path- 
ological relations  of  cholesterin),  the  necessary  conditions 
for  this  observation  seemed  to  be  fulfilled.  The  patient  suf- 
fered from  intense  jaundice  dependent  upon  obstruction 
of  the  common  bile  duct  from  duodenitis.  The  feces  were 
clay-colored.  After  a  time  the  patient  was  relieved  of  the 
jaundice,  and  the  feces  regained  their  natural  color.  While 
the  feces  were  decolorized  and  when  the  icterus  was  most 
marked,  it  is  probable  that  the  bile  was  entirely  cut  off 
from  the  alimentary  canal.  This  condition  was  relieved, 
however,  when  the  feces  regained  their  color  and  the  ic- 
terus disappeared.  For  the  purpose  of  ascertaining  the 
effect  of  the  obstruction  to  the  flow  of  bile  on  the  ster- 
corin of  the  feces  and  of  the  reestablishment  of  the  flow, 
the  stools  were  examined  chemically  during  the  jaundice 
and  after  the  patient  had  recovered. 

Analysis  of  Decolorized  Feces. — The  quantity  of 
feces  examined  was  941.4  grains.  After  evaporation,  ex- 
traction with  ether  and  extraction  of  the  residue  left  after 
the  evaporation  of  the  ether  with  hot  alcohol,  the  fat, 
which  was  very  abundant,  was  entirely  saponified  by  boil- 
ing for  fifteen  minutes  with  a  solution  of  caustic  potash,, 
showing  that  neither  cholesterin  nor  stercorin  was  present. 

Analysis  of  Feces  from  the  same  Patient  after 
they  had  become  Normal  in  Color. — This  was  made 
nineteen  days  after  the  preceding  analysis.  The  quantity 
of  feces  was  small.  The  specimen  was  treated  in  the  usual 
way,  showing  stercorin  in  the  following  proportion: 

Quantity  of  feces 502.00  grains. 

"     stercorin 0.34      " 

Taken  in  connection  with  the  facts  which  have  already 
been  cited  in  regard  to  the  discharge  of  cholesterin  by 
the  anus  when  digestion  is  not  going  on,  this  observation 
seems  to  establish  the  origin  of  stercorin.  It  is  produced 
by  a  transformation,  connected  with  the  digestive  act,  of 


NEW    FUNCTION   OF  THE    LIVER  217 

the  cholesterin  of  the  bile.  When  cholesterin  does  not 
find  its  way  into  the  ahmentary  canal,  as  was  the  case  in 
the  first  analysis  of  feces,  stercorin  is  not  found  in  the 
dejections;  when  the  discharge  is  reestablished,  the  ster- 
corin reappears. 

Comparison  of  the  Daily  Quantity  of  Stercorin 

DISCHARGED,  WITH  THE  QUANTITY  OF  ChOLESTERIN  PRO- 
DUCED BY  THE  Liver. — The  quantity  of  stercorin  which  I 
extracted  from  the  regular  daily  feces  of  a  healthy  adult 
male  was  10.417  grains.  As  there  is  no  cholesterin  found 
in  the  dejections,  this  should  represent  the  entire  quantity 
of  cholesterin  excreted  in  the  twenty-four  hours.  A  com- 
parison of  this  quantity  with  the  estimated  quantity  of  cho- 
lesterin discharged  in  the  day,  shows  this  to  be  the  case. 

Quantity  of  bile  in  the  twenty-four  hours  (Dalton) 16.940  grains.* 

"         "  cholesterin  at  0.618  pts.  per  1,000  (Flint) 10.469!    " 

"         "  stercorin  discharged  (Id.) 10.417      " 

Difference 052 

This  insignificant  difference  of  0.052  of  a  grain  shows 
at  once  the  correctness  of  the  estimate  of  the  daily  quan- 
tity of  bile  excreted,  the  accuracy  of  the  estimate  of  the 
proportion  of  cholesterin  in  the  bile  and  of  the  quantitative 
analysis  for  stercorin;  and  made,  as  the  three  observations 
were,  without  the  slightest  reference  to  each  other,  adds 
the  final  link  to  the  chain  of  evidence  in  support  of  the 
view  that  cholesterin,  in  its  passage  down  the  alimentary 
canal,  is  converted  into  stercorin,  in  which  form  it  is  dis- 
charged in  the  feces. 

The  history  of  cholesterin  thus  resolves  itself: 

1.  Cholesterin  is  an  efifete  material,  produced  by  the 
destructive  assimilation  of  nervous  matters  and  absorbed 
by  the  blood. 

2.  It  is  separated  from  the  blood  in  its  passage  through 
the  liver  and  enters  into  the  composition  of  the  bile,  giving 
this  fluid  its  excrementitious  character. 

3.  It  passes  with  the  bile  into  the  upper  part  of  the 
small  intestine,  when  the  process  of  'digestion  induces  a 
change  into  stercorin,  in  which  form  it  is  discharged  by 
the  feces. 

*  Dalton,  "  Treatise  on  Human  Physiology,"  2d  edition,  p.  171. 
f  See  table,  p.  173. 


2i8  NEW    FUNCTION   OF  THE    LIVER 

4.  Stercorin,  the  principal  excrementitious  constituent 
of  the  feces,  is  one  of  the  most  important  excretions  pro- 
duced by  the  waste  of  the  system. 

Pathological  Relations  of  Cholesterin. — With 
the  limited  data  on  the  subject  of  the  variations  in  the 
quantity  of  cholesterin  in  health  and  disease,  it  is  impos- 
sible to  do  more  than  merely  to  open  the  subject  of 
its  pathological  relations.  To  a  certain  extent,  all  ques- 
tions in  physiology  have  for  an  end  the  elucidation  of 
points  in  pathology.  The  practical  physician  who  may 
be  the  reader  of  this  article  will  naturally  inquire  if  the 
more  definite  views  which  we  are  now  enabled  to  hold  in 
regard  to  the  function  of  the  bile  are  of  any  use  to  him 
in  the  study  and  treatment  of  disease.  It  is  certain  that  no 
addition  to  a  knowledge  of  the  functions  of  the  healthy 
body  is  without  its  bearings  on  disease,  immediate  or  re- 
mote. What  may  seem  to  be  simply  a  matter  of  interest 
to  the  pure  physiologist,  without  apparently  any  practical 
bearing,  is  sure  at  some  time  to  become  so  connected 
with  other  advances  as  to  be  useful  to  the  practitioner. 
But  the  pathological  relations  of  an  important  excretion 
do  not  have  a  practical  interest  so  remote,  especially  when 
this  function  is  connected  with  the  liver.  Almost  from 
time  immemorial,  a  large  number  of  diseases  have  been 
referred  to  derangement  of  the  liver,  and  in  their  treatment, 
it  has  been  thought  of  immense  importance  to  promote 
the  secretion  of  the  bile.  A  certain  class  of  remedies  sup- 
posed to  regulate  the  secretion  of  bile  has  been  con- 
stantly employed  by  physicians.  x\t  the  present  day  these 
ideas  have  fallen  somewhat  into  disrepute;  for  the  enlight- 
ened physician  is  now  accustomed  to  base  his  pathological 
views  upon  a  certain  amount  of  definite  knowledge;  and 
it  has  been  found  that  both  the  physiology  and  the  pathol- 
ogy of  the  bile  have  been  very  little  understood.  The  older 
practitioners  had,  as  we  have  now,  a  certain  class  of  cases 
characterized  by  a  general  malaise,  and  having  indefinite 
symptoms  that  were  attributed  to  "  biliousness,"  in  which 
they  were  in  the  habit  of  employing  the  cholagogues,  with 
mercury  at  the  head,  with  undoubted  success.  It  is  true 
that  as  knowledge  of  disease  becomes  more  accurate,  the 
conditions  which  were  supposed  to  indicate  "  biliousness," 


NEW   FUNCTION   OF  THE    LIVER  219 

have  been  referred  to  other  disorders;  but  no  great  ad- 
vance has  been  made  in  the  pathology  of  the  hver,  and 
there  are  yet  many  conditions  which  may  be  successfully, 
though  empirically,  treated,  the  true  character  of  which 
is  unknown.  It  is  on  this  obscure  subject  that  it  is  hoped 
the  preceding  physiological  investigations  will  throw 
some  light.  To  repeat  a  comparison  made  use  of  before, 
a  knowledge  of  the  functions  of  cholesterin  and  its  history 
in  the  healthy  organism  should  contribute  as  much  to  the 
pathology  of  diseases  dependent  on  derangement  of  this 
function  as  the  development  of  the  functions  of  urea  has 
for  diseases  now  known  to  be  dependent  on  uremia. 

CHOLESTEREMIA 

In  common  with  other  excrementitious  substances, 
which  invariably  exist  in  the  blood  in  health,  if  the  func- 
tion of  the  eliminating  organ  is  interfered  with,  accumu- 
lation takes  place  in  the  blood.  This  has  already  been 
incidentally  referred  to  in  treating  of  the  properties  of 
cholesterin  w-hich  allied  it  to  effete  substances.  It  takes 
place  as  regards  urea;  but  cases  of  uremic  poisoning  oc- 
curred and  patients  died  in  uremic  coma,  long  before  the 
cause  of  it  was  understood.  It  is  the  same  with  the  bile. 
Ordinary  cases  of  jaundice,  which  have  been  called  by 
Piorry  cholemia,  are  not  of  a  dangerous  character;  but 
there  are  cases  in  which  jaundice,  though  less  marked  as 
regards  color,  is  a  very  different  condition.  Here  is  evi- 
dently the  operation  of  some  poison  in  the  blood;  and 
coma  and  death  from  its  efifects  on  the  brain  follow  as  in 
retention  of  the  urea.  Pathologists  inquire  why  there  is 
this  difference  in  the  severity  of  cases  of  icterus.  Chemists 
have  analyzed  the  blood  in  the  hope  of  explaining  it  by  the 
presence  of  the  glycocholates  and  taurocholates  of  soda  in 
the  grave  cases,  regarding  them  as  the  only  important 
constituents  of  the  bile;  but  their  failure  to  detect  these 
substances  has  left  the  question  still  unanswered. 

In  cases  of  simple  jaundice  there  is  a  resorption  of  the 
coloring  matter  of  the  bile  from  the  excretory  passages. 

In  cases  of  grave  jaundice,  which  almost  invariably  ter- 
minate fatally,  there  is  retention  of  cholesterin  in  the  blood, 
or  cholesteremia. 


220  NEW    FUNCTION   OF  THE    LIVER 

I  have  been  forced  to  make  use  of  cases  of  disease  ex- 
clusively in  studying-  this  condition,  for  no  one  has  yet 
been  able,  in  the  larger  animals,  to  extirpate  the  liver,  no- 
tice the  symptoms  of  poisoning  and  demonstrate  the  accu- 
mulation of  cholesterin  in  the  blood.  Nor  have  I  yet  been 
able,  on  account  of  the  insolul)ility  of  cholesterin,  to  make 
experiments  by  injecting  it  into  the  circulation.  I  had, 
however,  an  opportunity  of  making  an  examination  of  the 
blood  of  a  patient  in  the  last  stages  of  cirrhosis  of  the  liver 
accompanied  with  jaundice  and  compare  it  with  an  exam- 
ination of  the  blood  of  a  patient  suffering  from  simple  ic- 
terus. Both  of  these  patients  had  decoloration  of  the 
feces;  but  in  the  first,  the  icterus  was  a  grave  symptom, 
accompanying  the  last  stages  of  disorganization  of  the 
liver;  while  in  the  latter,  it  was  simply  dependent  on  duo- 
denitis, the  prognosis  was  favorable  and  was  verified  by 
the  result.  As  icterus  accompanying  cirrhosis  is  of  infre- 
quent occurrence,  I  deemed  myself  fortunate  in  having 
an  opportunity  to  compare  the  two  cases. 

Case  I.  Jaundice  Dependent  on  Obstruction  from  Duode- 
nitis.— Mary  Bishop,  ?et.  42,  native  of  Ireland,  widow,  occupation 
servant,  was  admitted  into  the  Blackwell's  Island  Hospital,  June  12, 
1862,  with  the  following  symptoms :  Slight  febrile  movement,  with 
severe  pains  over  the  duodenum ;  the  surface  of  the  body  was  high- 
ly icteric ;  the  stools  were  clay-colored ;  urine  high-colored,  but 
not  examined  for  bile ;  lungs  and  heart  normal ;  appetite  rather 
poor;  no  ascites.  The  icterus  had  existed  since  about  May  23, 
1862.    The  patient  was  confined  to  the  bed. 

Dr.  Flint,  the  visiting  physician,  pronounced  it  a  case  of  icte- 
rus dependent  on  duodenitis. 

Treatment. — Laxatives  daily,  with  good  diet  and  a  moderate 
quantity  of  stimulus. 

June  21.  A  small  quantity  of  blood  was  drawn  from  the  arm 
for  examination,  and  on  June  22,,  the  feces  were  collected  for  the 
same  purpose. 

June  27.     The  patient  remains  about  the  same. 

July  II.  All  pain  and  tenderness  over  the  duodenum  have 
disappeared.  She  has  steadily  improved  since  the  last  record.  The 
stools  have  been  natural  for  several  days.  Though  confined  to  the 
bed  most  of  the  time,  she  is  able  to  sit  up  two  or  three  hours  daily. 
The  jaundice  has  been  gradually  diminishing,  and  three  or  four 
days  ago  it  had  entirely  disappeared  and  is  now  absent. 

July  12.  Another  specimen  of  the  feces,  which  was  of  normal 
appearance,  was  taken  for  examination. 

Analysis  of  the  Blood  for  Cholesterin. — The  blood  was  ex- 
amined about  sixteen  hours  after  it  was  taken  from  the  arm.    It  had 


NEW    FUxNCTION   OF  THE    LIVER  221 

iully  separated  into  serum  and  clot.  The  serum  was  of  a  bright 
yellow  color,  more  markedly  bilious  than  in  the  succeeding  case. 
It  was  evaporated,  pulverized,  and  a  quantitative  analysis  for  cho- 
lesterin  made,  with  the  following  results: 

Quantity  of  blood 21 2.428  grains. 

Quantity  of  cholesterin o.  108      " 

Proportion  of  cholesterin  per  1,000  pts.  of  blood         0.508      " 

Case  II.  Jaundice  with  Cirrhosis. — Ann  Thompson,  ast.  39, 
native  of  Ireland,  occupation  servant,  was  admitted  into  the  Black- 
well's  Island  Hospital  June  16,  1862,  and  gave  the  following  his- 
tory: 

Three  months  ago  she  contracted  a  severe  cold,  which  was  ac- 
companied with  swelling  of  the  left  hand  and  of  both  legs,  continu- 
ing for  eight  or  nine  weeks.  At  the  end  of  that  time  she  noticed 
that  the  abdomen  was  increasing  in  size.  She  was  then  very  weak, 
the  urine  was  scanty,  bowels  regular  up  to  the  time  when  she 
entered  the  hospital.  She  denied  having  been  in  the  habit  of  drink- 
ing spirit,  but  acknowledged  that  she  drank  beer. 

June  18.  The  surface  of  the  body  was  icteric,  the  color  was 
very  marked  under  the  tongue  and  in  the  conjunctiva;  the  abdo- 
men was  full  of  fluid ;  pulse  90,  small  and  weak ;  bowels  loose  and 
the  dejections  clay-colored ;  the  urine  highly  tinged  with  bile  and 
copious ;  appetite  very  poor.  She  was  tapped,  and  about  eight 
quarts  of  clear,  straw-colored  serum  were  evacuated.  The  patient 
was  confined  to  the  bed. 

Dr.  Flint,  the  visiting  physician,  diagnosticated  cirrhosis. 

The  treatment  consisted  of  sustaining  measures,  with  stimu- 
lants and  the  tinct.  ferri  muriat. 

June  21.  A  small  quantity  of  blood  was  taken  from  the  arm 
for  examination,  and  on  June  23,  a  specimen  of  the  feces  was 
obtained  for  the  same  purpose. 

The  patient  died  June  27.  There  were  no  convulsions,  and  she 
was  sensible,  though  in  a  state  of  stupor,  up  to  twenty  minutes 
before  the  fatal  termination.  The  stupor  existed  three  or  four  days 
before  death.  Two  days  before,  she  complained  of  double  vision. 
The  icterus  was  excessive  up  to  the  time  of  her  death. 

Autopsy. — The  abdomen  contained  about  twelve  quarts  of 
liquid.  The  liver  was  examined.  Its  weight  was  3  lbs.  12J-  oz.  It 
was  very  light-colored,  and  had  something  of  the  "  hob-nail  "  ap- 
pearance, presenting,  in  short,  the  gross  characters  of  cirrhosis. 
The  gall-bladder  was  very  much  contracted  and  contained  only 
about  two  drachms  of  bile.  Microscopic  examination  of  the  organ 
showed  the  liver-cells  shrunken.  The  fibrous  substance  was  in- 
creased in  quantity,  and  there  were  present  a  large  number  of 
rather  angular  globules  of  fat. 

Analysis  of  the  Blood  for  Cholesterin. — The  blood  was  ex- 
amined about  sixteen  hours  after  it  was  drawn.  It  had  fully  sepa- 
rated into  serum  and  clot,  and  the  serum  was  of  a  greenish-yellow 
color.     The  whole,  serum  and  clot,  was  then  evaporated,  pulver- 


NEW    FUNCTION   OF  THE    LIVER 


ized,  and  a  quantitative  analysis  made  for  cholesterin  in  the  man- 
ner already  indicated,  with  the  following  results: 

Quantity  of  blood 50776  grains. 

Quantity  of  cholesterin 0.093      " 

Proportion  of  cholesterin  per  1,000  pts 1.850 

The  following  table  gives  a  comparison  of  these  results 
with  those  obtained  in  the  analyses  of  the  three  specimens 
of  healthy  blood  from  the  arm,  which  were  examined  at  the 
same  time,  and  all  five  specimens  subjected  to  identical 
processes. 

Table  of  Quantity  of  Cholesterin  in  Healthy  Blood,  Blood 
FROM  Simple  Jaundice,  and  Jaundice  with  Cirrhosis 

Blood  of  Jaundice 

Cholesterin 
per  1,000  pts. 

Case  I.  Simple  jaundice     0.508 
"    II.  Jaundice      with 

cirrhosis.  . .  .      1.850 


Healthy  Blood 

Cholesterin 
per  1,000  pts. 

Male,  aet.  35 0.445 

"     22 0.658 

"       "     24 0.751 


Case  I.  Simple   jaundice.       Percentage   of   increase  over 

minimum  of  healthy  blood.  I4-I57 

Decrease  below  maximum. . .  32.357 

Case  II.  Jaundice  with  cirrhosis.      Increase  over  minimum  315730 

Increase  over  maximum  146.338 

The  results  of  the  examination  of  the  blood  in  these 
cases  of  disease  are  striking  and  instructive.  It  has  al- 
ready been  seen  that  the  variations  in  health  are  very 
considerable.  In  the  three  analyses  here  noted,  the  maxi- 
mum was  0.751,  and  the  minimum  0.445  P^s.  per  1,000. 
The  conditions  which  regulate  this  variation  it  has  not  yet 
been  possible  to  study;  but  enough  is  known  in  regard 
to  it,  to  see  that  in  the  examination  of  blood  in  disease, 
the  cholesterin  must  mount  considerably  above  the  maxi- 
mum or  fall  much  below  the  minimum,  to  be  considered 
beyond  the  limits  of  health.  But  in  the  second  specimen 
of  jaundiced  blood,  the  variation  from  the  limits  of  health 
is  so  considerable  as  to  admit  of  important  physiological 
and  pathological  deductions. 

In  the  first  place,  what  is  the  bearing  of  these  observa- 
tions on  the  physiology  of  cholesterin?  As  before  re- 
marked, no  one  has  been  able  to  remove  the  liver  from  a 
living  animal  and  note  the  effect  upon  the  quantity  of  cho- 


NEW    FUNXTION   OF   THE    LIVER  223 

lesterin  in  the  blood.*  This  experiment,  if  it  were  possible, 
and  if  it  showed  that  cholesterin  increased  in  quantity  and 
killed  the  animal,  would  go  to  show  that  it  was  an  ex- 
crementitious  substance  and  that  it  was  removed  by  the 
liver.  But  while  the  experimental  physiologist  contributes 
much  to  the  information  of  the  pathologist  by  artificially 
producing  abnormal  conditions,  pathology  furnishes  a  mul- 
titude of  useful  experiments  of  Nature,  which  are  invalu- 
able to  the  physiologist.  In  the  present  instance,  cases  of 
disease  of  the  liver  present  a  condition  which  can  not  at 
present  be  imitated  by  experiments  on  the  lower  animals. 
Disorganizing  disease  of  the  liver  must  interfere  with  its 
excretory  function,  as  Bright's  disease  does  wdth  the  elim- 
ination of  urea;  and  if  cholesterin  is  an  excrementitious 
substance  to  be  removed  by  the  liver,  when  the  liver  is  seri- 
ously affected  with  structural  disease  there  should  be  an 
accumulation  of  it  in  the  blood.  This,  if  fully  established, 
is  positive  proof  of  the  character  of  cholesterin  and  the 
function  of  the  liver  connected  with  its  elimination. 

What  is  to  be  learned,  then,  from  a  comparison  of 
the  blood  in  Case  11.  of  jaundice  dependent  on  cirrhosis 
with  healthy  blood  and  a  study  of  the  history  of  the 
case? 

The  cholesterin,  in  this  instance,  is  enormously  in- 
creased in  quantity,  315.730  per  cent,  over  the  minimum, 
and  146.338  per  cent,  over  the  maximum.  The  case,  as 
far  as  symptoms  are  concerned,  was  of  a  very  grave  char- 
acter. The  patient  not  only  suffered  from  an  accumulation 
of  liquid,  but  there  was  evidently  a  poison  in  the  system. 
The  patient  died  after  three  or  four  days  of  stupor,  and  on 
post-mortem  examination  the  liver  was  found  disorgan- 
ized. There  was  a  deficient  secretion  of  bile,  and  had  been 
for  a  long  time;  for  the  gall-bladder  was  much  contracted 
and  the  stools  were  clay-colored.  In  short  the  patient 
died  of  cholesteremia;  and  the  fact  that  this  condition 
can  exist  is  a  proof  of  the  excrementitious  function  of 

*  Milller,  Kunde  and  Moleschott  have  succeeded  in  removing  the  liver 
from  frogs  and  keeping  them  alive  for  two  or  three  days — Moleschott  preserv- 
ing them  for  several  weeks.  These  observations  were  made  with  reference 
to  the  accumulation  of  the  biliary  salts  and  of  the  bile  pigment  in  the  blood, 
their  attention  not  having  been  directed  to  cholesterin.  I  began  a  series  of 
experiments  on  frogs,  but  they  promised  to  be  so  prolonged  that  they  were 
deferred. 


224  NEW    FUNCTION    OF    THE    LIVER 

cholesterin,  as  uremia,  as  a  toxemic  condition,  shows  that 
urea  is  an  excretion. 

Physiologically  considered,  this  case  fulfils  an  essential 
condition  of  excrementitious  substances;  namely,  accumu- 
lation in  the  blood  when  the  eliminating  functions  of  the 
excretory  organs  are  interfered  with.  The  liver  became  so 
disorganized  that  its  functions  were  seriously  disturbed, 
and  the  quantity  of  cholesterin  in  the  blood  increased  to 
a  very  great  extent. 

The  pathological  deductions  from  the  facts  which  have 
been  elicited  by  examinations  of  the  blood  in  these  cases 
seem  to  me  of  great  importance.  The  literature  of  diseases 
connected  with  disorders  of  the  liver  is  full  of  theories, 
more  or  less  plausible,  to  explain  certain  conditions  which 
have  long  been  established  by  clinical  observation.  There 
are  cases  of  simple  jaundice  which  are  not  dangerous  to 
life,  and  sometimes,  though  the  icterus  is  excessive,  run 
a  certain  course  without  interfering  even  with  the  ordinary 
vocations  of  the  patients.  Again,  there  is  jaundice  which 
is  invariably  fatal.  The  disease  described  by  Frerichs  un- 
der the  name  of  acute  atrophy  of  the  liver,  and  called  by 
some,  acute  jaundice,  is  one  of  the  most  serious  diseases 
of  which  there  is  any  knowledge.  The  existence  of  this 
great  difference  has  led  clinical  observers  to  attribute  the 
mild  cases  to  simple  resorption  of  the  coloring  matter  of 
the  bile,  and  the  severe  cases  to  a  retention  or  resorption 
of  some  of  its  more  important  constituents;  especially  as 
it  has  also  been  observed  that  the  symptoms  which  char- 
acterize the  latter  condition  occasionally  occur  in  struc- 
tural diseases  of  the  liver  without  any  discoloration  of  the 
skin.  But  the  pathology  of  this  disease  has  been  entirely 
unknown.  It  has  been  thought  that  in  such  cases  some 
of  the  elements  of  the  bile  should  exist  in  the  blood.  Fre- 
richs says:  "  In  the  same  way  that  urea  accumulates  in 
large  quantity  in  the  blood  in  granular  degeneration  of  the 
kidneys,  so  ought  the  biliary  acids  and  bile-pigment  to 
accumulate  in  the  blood  in  cases  of  granular  liver.  Re- 
peated observations  have  proved  that  this  is  not  the  case."  * 
Experiments  on  animals  have  been  followed  with  like  re- 

*  "  A  Clinical  Treatise  on  Diseases  of  the  Liver,"  by  Dr.  Fried.  Theod. 
Trerichs,  Professor  of  Clinical  Medicine,  etc..  Berlin.  Translated  by  Charles 
Murchison,  M.  D.     "  The  New  Sydenham  Society,"  London,  i860,  vol.  i.,  p.  83. 


NEW    FUNCTION   OF    THE    LIVER 


225 


suits.  The  frogs  that  were  kept  aHve  by  Moleschott  for 
weeks  after  the  removal  of  the  hver  did  not  present  a 
trace  of  the  biliary  salts  or  bile-pigment  in  any  part  of 
the  system,  showing  that  these  matters  are  manufactured 
in  the  liver.  This  obscurity,  which  leads  to  all  sorts  of 
theories  in  regard  to  liver-pathology,  must  exist  so  long 
as  our  knowledge  of  the  physiology  of  the  bile  is  so  in- 
definite. If  observers  had  looked  for  cholesterin,  a  sub- 
stance which  preexists  in  the  blood  and  is  separated  by 
the  liver,  instead  of  the  biliary  salts,  w^iich  do  not  pre- 
exist in  the  blood,  are  manufactured  in  the  liver,  as  these 
experiments  tended  to  show,  and  are  pecuHar  to  the  bile, 
they  would  have  met  with  different  results.  The  very  fact 
that  the  biliary  salts  are  peculiar  to  the  bile  and  found  in 
no  other  fluid  should  have  led  them  to  disregard  these  sub- 
stances in  their  analyses  of  the  blood,  because  this  stamps 
them  as  secretions  and  distinguishes  them  from  excretions. 
They  should  have  looked  for  some  substance  which  exists 
in  the  blood  as  well  as  the  bile,  an  indispensable  condition 
of  an  excretion,  and  this  substance  is  cholesterin. 

Understanding,  therefore,  the  physiological  relations  of 
cholesterin,  jaundice  may  be  divided  into  two  varieties: 
simple  icterus,  or  yellowness,  and  a  condition  which  I  have 
called  cholesteremia.  Cholesteremia  may  occur,  also,  with- 
out discoloration  of  the  skin. 

Simple  Icterus. — In  simple  icterus  there  is  a  resorp- 
tion of  the  coloring  matter  from  the  biliary  passages.  As 
it  has  been  shown  that  the  coloring  matter  of  the  bile 
appears  first  in  the  liver,  when  it  exists  in  the  blood  it  is 
not  due  to  accumulation  but  to  resorption.  In  these  cases 
the  resorption  is  generally  due  to  obstruction  of  the  biliary 
passages.  The  patient  suffers  only  from  the  disease  which 
causes  the  obstruction,  and  from  the  derangement  of  di- 
gestion which  is  due  to  the  absence  of  bile  from  the  intes- 
tinal canal.  In  those  cases  in  which  there  is  no  organic 
disease  of  the  liver,  there  is  no  danger  of  absorption  of 
cholesterin.  This  is  a  condition  analogous  to  retention  of 
urine.  The  patient  suffers  simply  from  retention  of 
bile  in  the  excretory  passages,  and  cholesteremia  is  no 
more  to  be  expected  from  obstruction  of  the  bile-duct 
without  structural  changes  of  the  liver,  than  uremia  is  to 
be  looked  for  in  vesical  retention  of  urine  without  organic 
15 


226  NEW   FUNCTION   OF  THE   LIVER 

change  in  the  kidneys.  Excretions  are  not  reabsorbed, 
akhough  they  may  be  retained  in  the  blood. 

The  quantity  of  cholesterin  in  the  blood  is  not  neces- 
sarily increased  in  simple  icterus;  for  the  liver  is  still  per- 
forming its  function  of  elimination,  and  when  once  sepa- 
rated from  the  blood  it  is  not  taken  up  again.  The  analysis 
of  the  blood  in  Case  I.  indicated  a  proportion  of  0.508 
parts  per  1,000,  which  is  within  the  limits  of  health,  a  little 
below  the  mean,  probably  on  account  of  the  somew'hat 
enfeebled  condition  of  the  patient. 

The  feces  may  or  may  not  be  decolorized,  this  depend- 
ing on  the  extent  of  the  obstruction  to  the  passage  of 
bile  into  the  intestine.  The  obstruction  to  the  flow  of  bile 
frequently  is  relieved  before  the  system  has  time  to  re- 
move the  coloration  of  the  skin,  and  the  feces  become  nor- 
mal while  the  patient  is  icteric.  In  some  instances  there 
is  no  change  in  the  appearance  of  the  dejections  during  the 
course  of  the  disease.  When  the  dejections  are  entirely 
decolorized  there  is  an  absence  of  stercorin,  into  which 
the  cholesterin  is  transformed  before  it  is  discharged,  with 
an  abnormal  quantity  of  fat  w-hich  has  passed  through  un- 
digested.* Stercorin  reappears  in  the  feces  when  the  flow 
of  bile  is  reestablished  and  they  assume  their  normal  color. 

The  two  following  analyses  were  made  of  the  feces  in 
Case  I.:  one,  when  they  were  entirely  decolorized  and  the 
patient  was  very  much  jaundiced,  and  the  other,  when  she 
had  recovered  and  the  dejections  had  assumed  their  nat- 
ural appearance. 

Feces  of  Case  I.  Jaundice  Dependent  on  Duodenitis.  First 
Analysis. — The  feces  were  clay-colored  and  apparently  free  from 
bile.  They  weighed  941.4  grains.  They  were  evaporated  to 
dryness  without  difficulty,  pulverized,  digested  with  f?iij  of  ether 
for  twenty  hours,  filtered  through  animal  charcoal,  evaporated  and 
extracted  with  hot  alcohol.  The  fatty  residue  after  evaporation 
of  the  alcohol  was  very  abundant. 

The  residue  was  then  treated  with  a  solution  of  caustic  potash 
and  exposed  to  a  gentle  heat.  In  fifteen  minutes  it  became  entirely 
saponified,  forming  a  clear  homogeneous  soap  with  no  residue, 
showing  the  absence  of  stercorin.     The  soap  was  boiled  down  and 

*  This  fact,  which  has  often  been  remarked,  seems  to  indicate  that  the  bile 
is  actively  concerned  in  the  digestion  of  the  fats.  I  have  noticed  that  dogs 
with  biliary  fistulae,  though  with  a  ravenous  appetite,  refuse  to  eat  fat  meat. 
This  disinclination  to  eat  fat  has  been  noticed  in  cases  of  jaundice  with  de- 
coloration of  the  feces. 


NEW    FUNCTION   OF  THE    LIVER  227 

molded  into  a  cake,  which  I  preserved  and  which  weighs  thirty- 
four  grains.     The  following  is  the  result  of  the  examination : 

Quantity  of  feces 94'  -4     grains. 

"fat 39- 1 24      " 

Percentage  of  fat 4- '  44 

No  stercorin  or  other  non-saponifiable  fats. 

Feces  Nineteen  Days  After.  Second  Analysis. — At  that 
time  the  patient  had  entirely  recovered  from  the  jaundice,  and 
the  feces  had  regained  their  natural  appearance.  A  small  speci- 
men was  taken  for  chemical  examination,  which  was  made,  em- 
ploying the  process  already  described  for  the  extraction  of  ster- 
corin, with  the  following  result: 

Quantity  of  feces 503         grains. 

"         "  stercorin 0.340      " 

Cholesteremia  with  Icterus. — In  jaundice  compli- 
cated with  blood-poisoning  there  exists  a  very  different 
state  of  things  as  regards  gravity  of  symptoms  and  prog- 
nosis. This  occurs  in  acute  jaundice,  or  when  it  accom- 
panies and  is  dependent  upon  structural  change  in  the 
liver,  as  the  jaundice  of  cirrhosis.  The  difference  in  the 
pathology  of  these  cases,  coinpared  with  those  of  simple 
icterus,  has  long  been  recognized;  but,  as  before  remarked, 
analysis  of  the  blood  has  failed  to  throw  any  light  on  the 
subject,  because  chemists  directed  their  attention  exclu- 
sively to  the  biliary  salts.     Frerichs  says: 

"  I  have  myself  repeatedly  examined  jaundiced  blood,  which 
has  been  obtained  by  venesection,  or  still  more  frequently,  from  the 
heart  or  vena  cavse  of  the  dead  body,  for  the  biliary  acids,  and 
their  immediate  derivatives ;  and  more  recently  I  have  had  it  ex- 
amined by  my  assistant.  Dr.  Valentin,  but  always  with  negative 
results.  No  substance  could  be  found  in  the  alcoholic  extract  of  the 
blood  which  yielded  any  indication,  by  Pettenkofer's  test  for  the 
biliary  acids,  whether  this  alcoholic  extract  was  treated  directly 
with  sulphuric  acid  and  sugar,  or  whether,  in  order  to  get  rid  of 
foreign  substances,  a  watery  extract  of  it  was  first  prepared.  This 
coincides  with  the  experience  of  most  of  the  older  observers."  * 

In  cases  of  blood-poisoning  by  retention  and  accumu- 
lation of  elements  of  the  bile  in  the  blood,  the  important 
pathological  condition  is  a  great  increase  in  the  quantity 
of  cholesterin.  The  fact  of  accumulation  of  this  substance 
in  the  blood  in  certain  cases  of  icterus,  has  been  noticed 
by  Becquerel  and  Rodier;  but  they  did  not  connect  it  with 
structural  change  in  the  liver  and  did  not  explain  its  physi- 

*  Frerichs,  op.  cii.,  p.  95. 


228  NEW   FUNCTION  OF  THE    LIVER 

ological  or  pathological  importance.  The  fact  of  its  accu- 
mulation in  the  blood  is  strong  evidence  of  its  excrcmenti- 
tious  character;  but  this  does  not  appear  to  have  attracted 
the  attention  of  the  observers  just  mentioned.  The  follow- 
ing is  one  of  the  cases  in  which  increase  of  cholesterin 
was  observed  by  them,  the  only  one  in  which  they  allude 
to  its  significance,  and  here  merely  to  state  their  inability 
to  explain  it: 

"  The  second  case  is  nearly  similar,  excepting  the  phlegmasia, 
which  did  not  exist.  It  relates  to  a  boy,  nineteen  years  of  age,  a 
li)iwnadicr,  affected  for  some  time  with  a  bilious  diarrhoea,  with 
fever,  and  icterus,  recently  developed  and  very  marked.  There 
existed  in  the  blood  of  this  patient  a  slight  diminution  of  the 
globules  (136)  ;  albumen  in  normal  quantity  (71.4)  ;  likewise  fibrin 
(2.3);  fatty  matter  sufficiently  abundant;  serolin  in  an  imponder- 
able quantity;  cholesterin  excessively  abundant  (0.798)  ;  soaps  abun- 
dant (2.032).  To  what  cause  must  we  attribute  this  great  quantity 
of  cholesterin?  How  and  why  is  it  concentrated  in  the  blood  in 
spite  of  the  biliary  flux?     This  is  what  it  is  difficult  to  decide."* 

What  I  have  shown  in  regard  to  the  physiology  of  cho- 
lesterin removes  the  difficulty  in  the  explanation  of  this 
fact.  In  Case  II.  there  was  the  rare  complication  of  jaun- 
dice with  cirrhosis,  the  symptoms  evidently  pointing  to 
poisoning  by  retention  of  some  toxic  element  in  the  blood. 
Examination  of  the  blood  in  this  case  showed  that  choles- 
terin existed  in  the  proportion  of  1.850  parts  per  1,000; 
the  minimum  of  healthy  blood  being  0.445  ^'^'^^  the  maxi- 
mum 0.751  parts.  Taking  this  case  as  an  example,  there 
is  cholesteremia  with  jaundice,  presenting  symptoms  which 
characterize  the  retention  of  bile  in  the  blood,  which  are 
already  well  known  and  were  established  long  before  it  was 
possible  to  say  what  toxic  element  was  retained.  Cases 
in  which  jaundice  exists  with  cholesteremia  are  so  different 
from  cases  of  ordinary  jaundice  that  there  is  no  difficulty 
in  making  the  discrimination  by  symptoms.  When  jaun- 
dice exists  with  cirrhosis,  it  is  probable  that  there  always  is 
cholesteremia.  In  aciite  jaundice  the  symptoms,  especially 
those  referable  to  the  nervous  system,  are  so  marked  that 
the  gravity  of  the  case  is  easily  recognized.  I  have  no 
doubt  that  in  such  cases  cholesterin  is  immensely  increased 
in  the  blood,  although  on  account  of  their  rarity  I  have 
not  had  an  opportunity  of  determining  this  by  analysis. 

*  Translated  from  Becquerel  and  Rodier,  op.  cit.,  p.  210. 


NEW    FUNCTION   OF  THE    LIVER  229 

Icterus  with  cholesteremia  and  simple  icterus  are  quite 
distinct  from  each  other.  The  only  feature  they  have 
in  common  is  the  discoloration  of  the  skin.  Simple  icterus, 
which  is  comparatively  harmless,  is  not  likely  to  run  into 
the  more  severe  variety,  which  can  not  occur  without  struc- 
tural change  in  the  liver;  while  the  grave  variety  occurs 
when  there  is  evidence  of  organic  disease  of  the  liver  or 
when  the  case  presents  symptoms  from  the  first  which  indi- 
cate its  serious  character.  The  one  has  no  more  constitu- 
tional danger  than  exists  in  a  simple  case  of  spasmodic 
retention  of  urine;  while  the  other  has  characters  as  grave 
as  those  which  attend  uremic  poisoning  due  to  disorgan- 
ization of  the  kidney. 

In  these  cases  the  feces  may  show  a  very  marked  de- 
ficiency of  bile;  but  this  is  due  to  the  deficient,  but  not 
arrested  secretion  of  this  fluid,  while  the  clay-colored  stools 
in  simple  icterus  are  dependent  on  the  want  of  discharge 
of  the  bile  into  the  intestine.  While  in  the  latter  instance, 
as  in  Case  I.,  one  would  expect  to  find  no  stercorin  in  the 
dejections,  in  the  former,  one  would  expect  to  find  ster- 
corin, though  in  greatly  diminished  quantity.  Further 
examination  of  the  feces  in  cases  of  structural  disease  of 
the  liver  will  be  of  advantage  as  indicating,  by  the  quan- 
tity of  stercorin  found,  the  extent  to  which  the  elimina- 
tive  function  of  the  liver  is  disturbed. 

The  following  analysis  was  made  of  the  feces  in  Case 
II.  of  jaundice  dependent  on  cirrhosis: 

Feces  of  Case  II.  Jaundice  Dependent  on  Cirrhosis. — The 
feces  were  clay-colored,  though  the  decoloration  was  not  quite  so 
marked  as  in  the  Case  I.  of  simple  jaundice. 

The  specimen  was  evaporated  with  great  difficulty.  It  was 
reduced  to  a  black,  glutinous  mass  which  could  not  be  pulverized. 
It  was  treated  twice  with  alcohol,  the  alcohol  evaporated,  and  once 
with  ether.  After  the  ether  had  evaporated  the  residue  was  pul- 
verized and  analyzed  for  stercorin,  with  the  following  result : 

Quantity  of  feces 272.  i      grains. 

Stercorin 0.077      " 

This  analysis  showed  a  very  great  diminution  in  ster- 
corin in  the  feces,  the  normal  quantity  in  the  daily  pas- 
sages, according  to  the  single  examination  I  have  made, 
being  10.417  grains.  The  specimen  of  feces  was  the  ordi- 
nary quantity  passed  daily.     It  showed  that  cholesterin 


230  NEW    FUNCTION   OF   THE    LIVER 

was  still  eliminated,  though  not  with  sufficient  activity  to 
prevent  its  accumulation  in  the  system.  This  was  further 
evidenced  by  the  post-mortem  examination,  when  the  gall- 
bladder was  foun(l  contracted  but  containing  a  small  quan- 
tity of  bile. 

Examination  of  the  blood  and  feces  of  the  patient  suf- 
fering from  cholcsteremia  with  jaundice  thus  leads  to  the 
following  conclusions: 

1.  Cholesterin  was  largely  increased  in  the  blood  show- 
ing that  the  structural  change  in  the  liver  had  interfered 
with  its  elimination. 

2.  Stercorin  was  correspondingly  diminished  in  the 
feces,  showing  that  the  cholesterin  was  not  discharged  in 
normal  quantity  into  the  alimentary  canal. 

Cholesteremia  without  Icterus. — From  a  practical 
point  of  view,  this  condition  is  one  which  it  is  very  im- 
portant to  be  able  to  recognize;  but  here  is  felt  most  the 
necessity  of  more  extended  investigations  than  it  has  been 
possible  to  make.  I  have  been  able  only  to  open  the 
subject  by  the  analysis  of  one  or  two  specimens  of  blood 
taken  from  patients  who  had  organic  change  in  the  liver, 
but  no  jaundice.  One  of  the  most  familiar  of  these  affec- 
tions of  the  liver  consists  in  those  changes  of  structure 
included  in  the  term  cirrhosis.  Frerichs  describes  a  con- 
dition which  he  calls  acholia,  denoting  suppression  of 
the  functions  of  the  liver.  This  is  the  condition  which 
I  have  called  cholesteremia,  which  expresses  the  con- 
stituent of  the  bile  which  produces  the  toxic  effects,  the 
action  of  which  was  unknown  to  Frerichs;  while  the  term 
acholia  expresses  retention  of  bile  without  giving  any 
idea  of  the  active  morbific  agent.  Further  investigation 
will  undoubtedly  establish  more  fully  what  the  analyses  I 
have  made  thus  far  seem  to  show;  namely,  that  in  what 
Frerichs  calls  acholia  without  jaundice,  there  is  the  choles- 
teremic  condition  that  exists  in  acholia  with  jaundice.  The 
following  quotation  from  Frerichs'  treatise  on  the  liver 
gives  an  idea  of  one  of  the  conditions  in  which  there  is 
acholia  (or  cholesteremia)  with  or  without  jaundice.* 

"  Cases  have  repeatedly  occurred  to  me,  in  which  individuals 
who  for  a  long  period  have  suffered  from  cirrhosis  of  the  liver, 

*  Frerichs,  op.  cit.,  p.  241. 


NEW    FUNCTION   OF  THE    LIVER  231 

have  suddenly  presented  a  series  of  symptoms  which  are  foreign 
to  that  disease.  They  have  become  unconscious,  and  have  been 
afterwards  seized  with  noisy  deHrium,  from  which  they  passed  to 
deep  coma,  and  in  this  state  have  died.  In  one  case  there  was 
spasmodic  contraction  of  the  muscles  of  the  left  side  of  the  face. 
In  most  cases,  slight  jaundice  made  its  appearance  at  the  same 
time,  and  in  one  instance  there  were  petechise.  Upon  post-mortem 
examination,  not  the  slightest  lesion  could  be  detected  in  the  brain, 
neither  were  there  indications  of  any  acute  disease  which  could 
account  for  the  derangement  of  the  cerebral  functions.  The  liver, 
in  all  cases,  presented  cirrhotic  degeneration  in  a  marked  degree, 
and  the  glandular  cells  were  for  the  most  part  loaded  with  fat ; 
large  quantities  of  leucine  separating  from  it ;  the  bile  ducts  con- 
tained only  a  small  quantity  of  pale  bile." 

In  certain  cases  of  organic  disease  of  the  liver,  and  prob- 
ably in  all  cases  accompanied  by  the  grave  symptoms  men- 
tioned by  Frerichs,  there  is  cholesteremia ;  but  this  charac- 
ter does  not  exist  in  all  cases  where  the  liver  is  affected, 
any  more  than  uremia  exists  in  all  cases  of  structural  dis- 
ease of  the  kidney.  Nature  not  only  provides  organs  which 
are  sufficient  for  the  removal  of  effete  matters  from  the 
blood,  but  provides  for  conditions  in  which  the  fimction  of 
these  organs  may  be  partly  interrupted,  and  yet  the  excre- 
tion go  on,  a  part  taking  on  the  function  of  the  whole. 
One  of  the  kidneys  may  be  removed,  and  yet  the  other, 
increased  in  size  it  is  true,  is  capable  of  performing  the 
function  of  both.  The  kidneys  may  be  partially  disorgan- 
ized, and  yet  the  sound  portion  be  sufficient  for  the  de- 
purative  function,  and  urea  will  not  accumulate  in  the 
blood.  So  it  is  with  the  liver.  There  are  patients  with 
partial  disintegration  of  this  organ,  as  in  some  cases  of 
cirrhosis,  suffering  apparently  but  little  inconvenience  from 
the  disease  and  presenting  none  of  the  symptoms  of  cho- 
lesteremia. But  when  the  liver  is  extensively  affected,  so 
much  so  that  it  can  not  separate  the  cholesterin  effectually 
from  the  blood,  there  is  cholesteremia.  I  have  made  an 
analysis  of  the  blood  of  two  patients  affected  with  cirrhosis 
who  presented  this  contrast  as  regards  the  symptoms  of 
cholesteremia.  In  one  of  them,  Case  III.,  there  was  con- 
siderable constitutional  disturbance;  and  in  the  other,  Case 
lY.,  the  patient  was  about  and  suffered  no  great  incon- 
venience, though  he  had  been  tapped  for  ascites  more 
than  thirty  times. 


232  NEW    FUNCTION   OF  THE    LIVER 

Case  III.  Cirrhosis  with  Ascites  and  Considerable  Affec- 
tion OF  the  General  Health. — Mary  Perkins,  ret.  23,  native  of 
Ireland,  prostitute,  has  been  a  spirit-drinker  for  about  seven  years. 
About  the  ist  of  May,  1862,  she  noticed  an  enhirgenient  of  the  ab- 
domen, which  was  accompanied  with  pain  over  the  region  of  the 
hver,  when  she  took  to  the  bed.  She  states  that  at  that  time  the 
stools  were  dark  green.  Fluid  continued  to  accumulate  in  the 
abdomen,  and  was  drawn  off  in  the  hospital  (Blackwell's  Island), 
June  25.  About  six  quarts  of  a  clear,  straw-colored  serum  were 
removed,  but  a  little  was  left  in  the  abdomen,  as  the  patient  was 
very  weak.  The  patient  improved  after  the  removal  of  the  fluid, 
which  did  not  reaccumulate  in  any  considerable  quantity.  The 
liver  was  found  diminished  in  size,  and  from  this  and  other  cir- 
cumstances, the  diagnosis  was  cirrhosis. 

June  28.  A  specimen  of  blood  was  taken  from  the  arm  for 
examination.  She  left  the  hospital  July  6,  and  was  confined  to  the 
bed  until  within  a  few  days  of  her  discharge. 

Analysis  of  the  Blood  for  Cholesterin. — The  blood  pre- 
sented nothing  peculiar  in  its  appearance.  A  quantitative  analysis 
W'as  made  for  cholesterin,  with  the  following  result : 

Quantity  of  blood 1 17-193  grains. 

"         "  cholesterin o.  108      " 

Proportion  of  cholesterin  per  1,000  pts.  of  blood         0.922      " 

Case  IV.  Cirrhosis  with  Ascites  and  Slight  Constitu- 
tional Disturbance. — Thomas  Hughes,  ?et.  about  33,  brewer,  pre- 
sented himself  at  the  Long  Island  College  Hospital,  July  i,  1862, 
with  Dr.  Dugan,  of  Williamsburg.  He  confessed  that  he  had  been 
in  the  habit  of  drinking  more  or  less  spirit  daily  for  the  past  ten 
years.  The  abdomen  began  to  swell  about  eighteen  months  ago. 
The  ascites  was  preceded  by  hematemesis,  when  he  vomited  an 
abundance  of  black,  clotted  blood.  The  belly  immediately  began  to 
swell  and  enlarged  rapidly.  He  took  hydragogues  under  the  direc- 
tion of  a  physician,  and  the  dropsy  disappeared,  but  returned  when- 
ever the  medicines  were  discontinued.  Qidema  of  the  lower  limbs 
occurred  soon  after  the  ascites.  He  has  had  recurrence  of  hema- 
temesis twice  since  the  first  attack. 

He  was  first  tapped  two  or  three  months  after  the  affection 
occurred  and  has  been  tapped  about  thirty  times  since.  He  was 
tapped  last  on  June  27th.  He  is  tapped  and  goes  out  the  next  day. 
He  thinks  nothing  of  it  and  is  always  for  the  time  relieved.  He 
has  continued  to  drink  beer  daily  and  some  spirit.  After  tapping 
his  appetite  is  good,  and  food  occasions  no  inconvenience.  When 
the  abdomen  is  full,  food  occasions  a  distressing  distention,  so  that 
he  does  not  eat  freely. 

The  urine  is  scanty  when  the  abdomen  is  full,  and  is  free  after 
tapping. 

There  is  no  pain  in  the  belly  or  elsewhere.  He  is  about  all 
day  but  is  not  engaged  in  business.  He  says  he  is  not  very  feeble.. 
He  presents  a  notably  anemic  aspect. 

The   abdomen  is   now  moderately   full    (July    l).      Superficial 


NEW    FUNCTION    OF  THE   LIVER  233 

veins  of  abdomen  much  enlarged.  Heart  appears  not  enlarged;  a 
feeble  systolic  murmur  over  the  body  of  the  organ. 

Several  months  before  the  ascites  began,  he  got  into  a  fracas 
and  was  badly  beaten.  He  v^as  not  laid  up,  but  says  he  did  not 
feel  w^ell  afterward  and  is  disposed  to  attribute  his  disease  thereto. 

Advised  to  continue  to  tap  when  the  abdomen  refills,  with 
tonics,  hygienic  measures,  and  abstinence  from  spirit,  continuing 
the  use  of  ale  moderately.     (Private  records  of  Dr.  Flint.) 

July  I.  A  specimen  of  blood  was  taken  from  the  arm  for  ex- 
amination. 

Analysis  of  the  Blood  for  Cholesterin. — The  blood  was 
treated  in  the  usual  way,  and  a  quantitative  analysis  was  made  for 
cholesterin,  with  the  following  result: 

Quantity  of  blood 251.567  grains. 

"         "  cholesterin 0.962      " 

Proportion  of  cholesterin  to  1,000  pts.  of  blood.         0.246      " 

The  following  table  shows  the  comparative  quantity  of 
cholesterin  in  these  specimens  and  in  the  three  specimens 
of  healthy  blood: 


Healthy  Blood 

Cholesterin 
per  1,000  pts. 

Male,  aet.  35 0.445 

"       "     22 0.658 

"      "     24 0.751 


Blood  of  Cirrhosis 

Cholesterin 
per  1,000  pts. 

Case  III.  Cirrhosis    (se- 
vere)       0.922 

Case  IV.  Cirrhosis  (mild)    0.246 


Case  III.     Cirrhosis  (severe).     Percentage   of  increase   in 

cholesterin  over  minimum 

of  healthy  blood 107.190 

Ditto  over  maximum 22.769 

Case   IV.     Cirrhosis   (mild).      Percentage  of  decrease  in 

cholesterin    below    mini- 
mum of  healthy  blood. . .       42.469 

These  two  cases  present  a  very  striking  contrast;  and 
the  chemical  examination  of  the  blood  has  shown  as 
marked  a  difference  in  the  quantity  of  cholesterin  as  in 
the  gravity  of  the  attendant  symptoms.  They  teach,  how- 
ever, an  important  lesson.  There  is  not  always  an  accu- 
mulation of  cholesterin  in  the  blood  when  the  structure 
of  the  liver  is  altered,  it  being  requisite  that  this  alteration 
should  involve  enough  of  the  organ  to  interfere  with  the 
elimination  of  this  substance.  The  quantity  may  even  fall 
below  the  natural  standard  in  a  patient  who  is  rendered 
anemic  by  the  consequences  of  a  cirrhosis  which  is  not 
sufficient  to  induce  cholesteremia.  The  process  of  nutri- 
tion being  thereby  diminished  in  activity,  the  production 


234  NEW    FUNCTION   OF    THE    LIVER 

of  this  substance,  by  destructive  assimilation,  is  necessarily 
diminished.  The  cholesteremia  may  be  slight  and  tran- 
sient; for  the  causes  which  produce  it  may  be,  to  a  certain 
extent,  temj^orary.  In  Case  III.  the  patient  was  confined 
to  the  bed,  suffering  acute  pain  over  the  region  of  the  liver, 
in  all  probability  due  to  a  slight  degree  of  inflammation. 
This  interfered  with  the  excretion  of  cholesterin,  and  its 
proportion  in  the  blood  was  increased  to  22.769  per  cent, 
over  the  maximum,  and  107.190  over  the  minimum.*  As 
the  patient  was  somewhat  enfeebled  by  syphilis  before  the 
symptoms  of  disease  of  the  liver  made  their  appearance, 
it  is  probable  that  the  quantity  of  cholesterin  in  the  blood 
did  not  equal  the  highest  standard  in  health.  At  all 
events,  there  was  a  notable  increase  even  over  the  maxi- 
mum quantity.  Case  IV.  is  not  less  instructive.  Here 
is  a  patient  who  has  had  cirrhosis  of  the  liver,  with  ascites, 
for  eighteen  months,  and  has  been  tapped  more  than  thirty 
times.  He  apparently  has  suffered  from  nothing  more  than 
the  mechanical  effects  of  the  liquid,  which  has  interfered 
at  times  with  digestion,  and  rendered  him  anemic.  He  is 
tapped  and  immediately  relieved,  going  out  the  next  day. 
There  seems  to  be  no  interference  with  the  functions  of  the 
liver,  so  far  as  the  symptoms  are  concerned,  other  than 
the  mechanical  obstruction  to  the  circulation;  and  the 
case,  as  regards  symptoms,  resembles  cases  of  ovarian 
dropsy  where  the  patient  carries  about  an  immense  quan- 
tity of  water,  but  suffers  only  from  this,  and  is  relieved 
temporarily  when  the  water  is  removed.  Considering 
the  condition  of  the  patient,  one  should  not  be  surprised 
to  find  the  cholesterin  of  the  blood  not  increased,  but  di- 
minished in  quantity;  and  one  may,  I  think,  come  to  the 
conclusion  from  the  symptoms  as  well  as  the  analysis  of 
the  blood,  that  though  the  liver  was  affected  sufficiently 
to  produce  obstruction  of  the  circulation,  there  w^as  not 
sufficient  disease  to  give  rise  to  cholesteremia. 

It  is  evident  that  much  more  extended  observations  are 
necessary  in  order  to  establish  the  clinical  relations  of  cho- 
lesteremia without  jaundice;  but  the  case  of  Mary  Perkins 
shows  that  this  condition  does  exist,  while  the  case  of 
Thomas  Hughes  shows  that  it  does  not  follow  structural 

*  Unfortunately  the  character  of  the  stools  was  not  noted. 


NEW    FUNCTION    OF  THE    LIVER 


235 


Table  of  Quantitative  Analyses  for  Cholesterin 


Human  blood  from  the  arm.  Healthy  male  set.  35 

"  "  "      xt.  22 

"  "  "  "  "      ret.  24 

"  "  "  Simple  jaundice 

"  "  "  Cholesteremia  with  jaundice 

"  "  "  Cirrhosis  (grave) 

"  "  «'  "         (mild) 

"  "  "  Hemiplegia — 

Case      I.  Paralyzed  side. 

Sound  side  .  .  . 

Case    II.   Paralyzed  side. 

Sound  side  .  . . 

Case  III.   Paralyzed  side. 

Sound  side  .  .  . 

Blood  from  carotid  ) 

"         "      internal  jugular  \  Dog  experiment 

"         "      femoral  vein        ) 

"         ;;      carotid  ( j3      experiment  \ 

"         "      mternal  jugular  )        •=      ^  ( 

"  "      carotid  ) 

"         "      internal  jugular  >  Dog  experiment 

"         "      femoral  vein        ) 

"         "      carotid  ) 

"         "      portal  vein  >  Dog  experiment 

"         "      hepatic  vein         ) 

Human  brain  (subject  killed  instantly) 

"      (Case  n.,  killed  instantly) 

Human  bile  (specimen  from  Case  II.) 

Crystalline  lens  (4  lenses  from  the  ox) 

Meconium 


Quantity 

Cholesterin 

examined. 

peri,ooopts. 

grains. 

312.083 

0.445 

187.843 

0.658 

102.680 

0-751 

212.428 

0.508 

50.776 

1.850 

117-193 

0.922 

251.567 

0.246 

55-458 

128.407 

0.481 

18.381 

66.396 

0.808 

21.824 

52.261 

0.579 

179.462 

0.774 

134.780 

0.801 

133.886 

0.806 

140.847 

0.768 

97.811 

0.947 

143.625 

0.967 

29.956 

1-545 

45-035 

1.028 

159-537 

1-257 

168.257 

1.009 

79.848 

0.964  ■ 

159-753 

7.729 

150.881 

11.456 

224.588 

0.618 

135.020 

0.907 

170.541 

6.245 

change  in  the  Hver  unless  the  lesion  is  extensive.  The 
fact  that  there  may  be  contamination  of  the  blood  by  the 
retention  of  a  biliary  matter,  without  discoloration  of  the 
skin,  is  exceeding  important;  and  of  this  there  seems  to  me 
to  be  no  doubt.  A  patient  who  has  structural  disease  of 
the  liver  and  presents  symptoms  of  blood-poisoning  is  suf- 
fering from  cholesteremia,  although  there  is  no  icterus. 
The  cholesteremia  may  vary  in  degree  between  the  mild- 
ness which  characterized  Case  IIL,  in  which  it  was,  per- 
haps, temporary,*  and  the  grave  condition  mentioned  by 
Frerichs,  characterized  by  noisy  delirium  and  coma,  and 
announcing  a  speedy  fatal  termination.     Adding  to  these 


*  The  patient  having  gone  out  of  the  hospital,  it  was  impossible  to  settle 
this  point. 


236  NEW   FUNCTION  OF  THE   LIVER 

conditions  the  cases  of  what  is  ordinarily  called  bilious- 
ness, attended  with  drowsiness,  an  indefinite  feeling  of 
malaise,  constipation,  etc.  (and  all  this  relieved  by  a  simple 
mercurial  purge,  which  is  said  to  promote  the  secretion 
of  the  liver),  is  it  not  to  be  hoped  that  some  light  will  be 
thrown  on  their  pathology  by  a  knowledge  that  there  is  a 
condition  called  cholesteremia!  As  yet  this  is  but  specu- 
lation; but  the  discovery  of  the  important  function  of  cho- 
lesterin  opens  a  wide  field  of  inquiry  in  this  direction;  and 
ere  long  the  physician  may  be  able  to  speak  of  ''  bilious- 
ness," and  "  liver  complaint,"  with  some  definite  ideas  of 
their  pathology. 

The  table  on  page  235  gives  the  results  of  the  quanti- 
tative analyses  for  cholesterin  which  have  been  referred 
to  in  this  article. 

CONCLUSIONS 

The  observations  contained  in  the  preceding  article 
seem  to  me  to  justify  the  following  conclusions: 

1.  Cholesterin  exists  in  the  bile,  the  blood,  the  nervous 
matter,  the  crystalline  lens  and  the  meconium,  but  does 
not  exist  in  the  feces  under  ordinary  conditions.  The 
quantity  of  cholesterin  in  the  blood  of  the  arm  is  five  to 
eight  times  more  than  the  ordinary  estimate. 

2.  Cholesterin  is  formed,  in  great  part  if  not  entirely,, 
in  the  substance  of  the  nervous  matter,  where  it  exists  in 
great  abundance,  from  which  it  is  taken  up  by  the  blood 
and  constitutes  one  of  the  most  important  of  the  effete 
or  excrementitious  products  of  the  body.  Its  formation 
is  constant,  and  it  always  exists  in  the  nervous  matter  and 
the  circulating  fluid. 

3.  Cholesterin  is  separated  from  the  blood  by  the  liver, 
appears  as  a  constant  constituent  of  the  bile  and  is  dis- 
charged into  the  alimentary  canal.  The  history  of  this 
substance,  in  the  circulating  fluid  and  in  the  bile,  marks  it 
as  a  product  destined  to  be  discharged  from  the  body,  as 
an  excretion.  It  preexists  in  the  blood,  subserves  no  useful 
purpose  in  the  economy,  is  separated  by  and  not  formed  in 
the  liver,  and  if  this  separation  is  interfered  with,  it  accu- 
mulates in  the  system. 

4.  The  bile  has  two  separate  and  distinct  functions  de- 
pendent on  the  presence  of  two  constituents  of  entirely 


NEW   FUNCTION   OF  THE    LIVER  237 

different  characters.  It  has  a  function  connected  with  nu- 
trition. This  is  dependent  on  the  presence  of  the  glyco- 
cholate  and  taurocholate  of  soda,  which  do  not  preexist 
in  the  blood,  subserve  a  useful  purpose  in  the  economy 
and  are  not  discharged  from  the  body,  are  found  in  the 
liver  and  peculiar  to  the  bile,  do  not  accumulate  in  the 
blood  when  the  function  of  the  liver  is  interfered  with,  and 
are,  in  short,  products  of  secretion.  The  bile  has  another 
function  connected  with  depuration,  which  is  dependent 
on  the  presence  of  cholesterin,  which  is  an  excretion. 
The  flow  of  the  bile  is  remittent,  being  much  increased 
during  the  digestive  act,  but  produced  during  the  intervals 
of  digestion  for  the  purpose  of  separating  cholesterin  from 
the  blood. 

5.  The  ordinary  normal  feces  do  not  contain  choles- 
terin, but  contain  stercorin — formerly  called  serolin,  from 
its  being  supposed  to  exist  only  in  the  serum  of  the  blood. 
Stercorin  results  from  a  transformation  of  the  cholesterin 
of  the  bile  during  the  digestive  act. 

6.  The  change  of  cholesterin  into  stercorin  does  not 
take  place  when  digestion  is  arrested  or  before  this  pro- 
cess begins;  consequently,  stercorin  is  not  found  in  the 
meconivmi  or  in  the  feces  of  hibernating  animals  during 
their  torpid  condition.  These  matters  contain  cholesterin 
in  large  abundance,  which  also  sometimes  appears  in  the 
feces  of  animals  after  a  prolonged  fast.  Stercorin  is  the 
form  in  which  cholesterin  is  discharged  from  the  body. 

7.  The  difference  between  the  two  familiar  varieties 
of  jaundice,  one  characterized  only  by  yellow-ness  of  the 
skin  and  comparatively  innocuous,  while  the  other  is  at- 
tended with  very  grave  symptoms  and  is  almost  invariably 
fatal,  is  dependent  upon  the  obstruction  of  the  bile  in 
one  case  and  its  suppression  in  the  other.  In  the  first  in- 
stance, the  bile  is  confined  in  the  excretory  passages  and  its 
coloring  matter  is  absorbed;  while  in  the  other,  cholesterin 
is  retained  in  the  blood. 

8.  There  is  a  condition  of  the  blood  dependent  upon 
the  accumulation  of  cholesterin  which  I  have  called  clioles- 
teremia.  This  occurs  only  when  there  is  structural  change 
in  the  liver,  which  incapacitates  it  from  performing  its  ex- 
cretory function.  It  is  characterized  by  symptoms  of  a 
grave  character,  referable  to  the  brain,  and  probably  is 


238  NEW   FUNCTION    OF  THE   LIVER 

dependent  upon  the  effects  of  the  retained  cholesterin  on 
this  organ.     It  occvirs  with  or  without  jaundice. 

9.  Cholesteremia  does  not  occur  in  all  cases  of  struc- 
tural disease  of  the  liver.  Enough  of  the  liver  must  be 
destroyed  to  prevent  the  due  elimination  of  cholesterin. 
In  cases  in  which  the  organ  is  but  moderately  affected,  the 
sound  portion  is  capable  of  performing  the  eliminative 
function  of  the  whole. 

10.  In  cases  of  simple  jaundice,  when  the  feces  are  de- 
colorized and  the  bile  is  entirely  shut  off  from  the  intestine, 
stercorin  is  not  found  in  the  evacuations;  but  in  cases  of 
jaundice  with  cholesteremia,  stercorin  may  be  found, 
though  always  very  much  diminished  in  quantity,  showing 
that  there  is  an  insufficiency  in  the  separation  of  the  cho- 
lesterin from  the  blood,  although  its  excretion  is  not  en- 
tirely suspended.  After  death,  but  a  small  quantity  of  bile 
is  found  in  the  gall-bladder. 


PLATE    I 


Fig.  4. 


Fig.  5. 


PLATE    II 


I6 


Fig.  9. 


Fig.  10. 


PLATE    III 


Fig.  14. 


Fig.  15. 


EXPLANATION   OF  THE  PLATES 

Fig.  I. — Cholesterin  extracted  from  meconium.     j\  inch  objective. 

Fig.  2. — Stercorin  and  fatty  matters  from  the  blood  of  the  carotid 
artery.     ^  inch  objective. 

Fig.  3. — Cholesterin  and  small  broken  crystals  of  stercorin  from 
the  same  specimen  of  blood  from  the  carotid,  examined 
eleven  days  after.     Nachet,  No.  3  objective. 

Fig.  4. — Cholesterin  from  the  brain.     \  inch  objective. 

Fig.  5. — Cholesterin  from  the  blood  of  the  internal  jugular,  with 
a  few  needles  of  stercorin.     ^  inch  objective. 

Fig.  6. — Cholesterin  and  stercorin  from  the  same  extract  as  Fig.  5, 
examined  the  next  day.    ^  inch  objective. 

Fig.  7. — Cholesterin  and  stercorin  from  the  blood  of  the  vena  cava. 
^  inch  objective. 

Fig.  8. — Cholesterin  from  the  blood  of  the  portal  vein.  A  inch 
objective. 

Fig.  9. — Cholesterin  from  the  blood  of  the  hepatic  artery.  -J  inch 
objective. 

Fig.  10. — Cholesterin  and  stercorin  from  the  blood  of  the  hepatic 
artery,    i  inch  objective. 

Fig.  II. — Fatty  substances  from  the  blood  of  the  hepatic  vein.  ^ 
inch  objective. 

Fig.  12. — Cholesterin  and  stercorin  from  the  same  specimen,  ex- 
amined the  following  day.     -|  inch  objective. 

Fig.  13 — Cholesterin  extracted  from  bile,     i  inch  objective. 

Fig.  14. — Stercorin  from  human  feces.     -j-V  inch  objective. 

Fig.  15. — Stercorin  from  the  same  specimen,  after  it  had  been 
melted,  placed  on  a  glass  slide,  covered  with  thin  glass, 
and  allowed  to  crystallize.  The  crystallization  was 
very  slow,  occupying  some  weeks.  This  Fig.  shows 
splitting  of  the  borders  and  points  of  the  crystals  with 
the  globules  referred  to  on  page  207.  The  globules 
were  of  variable  size,  and  some  of  them  were  arranged 
in  rows,  which,  with  an  inferior  microscope,  might  be 
mistaken  for  varicosities  on  the  needles.  From  their 
appearance  in  this  specimen,  after  it  had  been  thor- 
oughly purified,  I  am  inclined  to  change  the  opinion 
expressed  on  page  207,  and  regard  them  as  composed 
of  stercorin  and  not  fatty  impurities.     ^  inch  objective. 


X 

THE  EXCRETORY  FUNCTION  OF  THE  LIVER 

Published  in  the  "  Transactions  of  the  International  Medical  Congress,"  held 
in  Philadelphia  in  September,  1876. 

I  HAVE  selected  as  the  subject  which  I 'shall  have  the 
honor  to  present  to  the  Section  on  Biology,  the  Excretory- 
Function  of  the  Liver,  for  the  reason  that  it  seemed  to  me 
better  to  discuss  a  question  concerning  which  I  had  made 
personal  and  original  investigations  than  to  recite  the  ob- 
servations of  others,  however  interesting  and  important 
the  latter  might  be.  I  have  ventured  to  assume  that  the 
views  which  I  have  to  offer  are  not  without  importance; 
.and  they  are  certainly  not  so  familiar  as  many  other  topics 
which  I  might  with  propriety  have  selected.  I  shall,  there- 
fore, endeavor  to  bring  to  your  notice,  in  the  simplest  man- 
ner possible,  what  I  have  myself  learned  in  regard  to  the 
liver  as  an  organ  of  excretion. 

It  is  now  well  known  that  the  liver  has  a  variety  of 
important  functions  with  which  physiologists  are  more  or 
less  acquainted.  The  liver  produces  a  substance  which 
is  converted  into  sugar  and  is  carried  away  in  the  torrent 
of  the  circulation.  It  secretes  bile  which  performs  an  im- 
portant office  in  digestion.  In  addition  to  the  digestive 
function  of  the  bile.  I  think  I  have  shown  that  this  fluid 
serves  as  the  vehicle  for  the  elimination  of  at  least  one 
excrementitious  matter,  which  is  discharged  in  a  modi- 
fied form  in  the  feces.  If  the  liver  serves  as  an  organ  of 
excretion,  it  is  evidently  of  great  importance,  from  a  path- 
ological as  well  as  a  physiological  point  of  view,  to  arrive  at 
an  accurate  knowledge  of  the  mechanism  of  this  function. 
For  a  long  time,  many  pathological  conditions  have  been 
attributed  to  defective  or  perverted  action  of  the  liver; 
but  the  terms,  "  liver  complaint,"  "  biliousness,"  etc.,  have 
failed  to  convey  any  definite  pathological  idea,  and  it  is 

239 


240       EXCRETORY    FUNCTION    OF  THE    LIVER 

probably  true  that  the  liver  has  been  accused  of  many 
sins  of  omission  and  commission  without  any  positive 
scientific  reason.  Many  medical  writers  have  assumed,  in 
an  indefinite  way,  that  the  liver  possesses  an  excretory 
function;  but  so  far  as  I  know,  no  physiologist  has  de- 
scribed any  definite  excrementitious  substance  eliminated 
by  this  organ  prior  to  my  observations  in  1862. 

There  are  certain  general  laws  applicable  to  secretions 
and  to  excretions,  which  it  is  important  to  consider  in  dis- 
cussing the  functions  of  the  bile: 

I.  Secretions  have  some  useful  purpose  to  serve  in  the 
economy,  and. as  a  rule  they  are  not  discharged  from  the 
body  in  health.  Excretions  have  no  function  in  the  econ- 
omy and  are  discharged  from  the  body. 

II.  The  flow  of  secretions  from  the  glands  usually  is 
intermittent,  occurring  when  their  function  is  called  into 
action.  The  flow  of  excretions  usually  is  either  constant 
or  remittent. 

III.  The  production  of  excretions  depends  upon  the 
general  process  of  disassimilation,  which  is  constant.  The 
production  of  secretions  has  no  relation  to  disassimilation, 
but  is  connected  with  processes  which  usually  take  place 
at  intervals. 

IV.  The  elements  of  secretion,  which  give  to  secreted 
fluids  their  characteristic  physiological  properties,  are 
formed  de  novo  in  the  glands  themselves  out  of  materials 
furnished  by  the  blood,  and  they  do  not  preexist  ready- 
formed  in  the  circulating  fluid.  The  elements  of  excretion 
preexist  in  the  blood,  being  taken  up  by  the  lymph  or  by 
the  blood  from  the  tissues,  and  they  are  separated  from 
the  blood  by  organs  which  have  no  part  in  their  actual  pro- 
duction; except  that  excrementitious  substances  may  be 
changed  one  into  another,  as  creatin  into  creatinin  or  uric 
acid  into  urea. 

V.  When  secreting  organs  are  removed  or  destroyed, 
there  is  no  vicarious"  production  of  the  peculiar  constitu- 
ents of  the  secretions;  these  elements  do  not  accumulate 
in  the  blood;  and  the  system  suffers  simply  from  the  ab- 
sence of  the  function  of  the  special  secretion.  When  ex- 
creting organs  are  removed  or  destroyed,  there  may  be  a 
vicarious  elimination  of  the  excrementitious  matters  by 
other  organs  or  the  system  may  suffer  toxic  effects  from 


EXCRETORY   FUNCTION    OF  THE    LIVER       241 

the  accumulation  of  excrementitious  matters  in  the  circu- 
lating fluid. 

VI.  The  characteristic  constituents  of  true  secretions 
generally  are  reabsorbed  by  the  blood;  but  they  are  taken 
up  in  a  modified  form,  so  ihat  they  are  not  to  be  recog- 
nized in  the  circulating  fluid.  Elements  of  excretion  are 
with  difficulty  reabsorbed  by  the  blood  after  they  have 
once  been  separated  by  the  proper  organs. 

The  applications  of  the  foregoing  general  laws  may  be 
readily  made  to  the  pancreatic  juice  as  contrasted  with  the 
urine,  which  two  fluids  may  be  taken  as  types  respectively 
of  secretions  and  of  excretions.  Before  making  an  appli- 
cation of  these  laws  to  the  bile,  we  may  consider  the  simple 
question  as  to  whether  it  can  be  shown  that  this  fluid  has 
a  useful  function  to  perform  as  a  secretion.  If  the  bile 
has  no  such  function,  an  animal  would  live  and  maintain 
its  normal  condition  when  the  bile  is  diverted  from  the  in- 
testine and  discharged  from  the  body.  This  question  has 
been  made  the  subject  of  experimental  observation  by 
simply  cutting  off  the  bile-duct  and  making  a  fistula  into 
the  gall-bladder,  by  which  the  bile  is  discharged.  The  oper- 
ative procedure  involved  is  not  difficult,  but  is  very  likely 
to  be  followed  by  fatal  peritonitis,  so  that  few  experiments 
of  this  kind  have  succeeded.  In  the  experiments  which 
have  succeeded,  in  the  hands  of  Schwann,  Bidder  and 
Schmidt,  Nasse,  Bernard  and  myself,  the  dogs  have  lived 
for  thirty  or  forty  days,  dying  with  all  the  symptoms  of 
inanition.  In  one  remarkably  successful  experiment  per- 
formed by  myself,  the  dog  lived  for  thirty-eight  days,  had 
a  voracious  appetite  and  died  at  the  end  of  that  period 
after  having  lost  about  four-tenths  of  his  weight.  In  this 
experiment  the  bile-duct  was  ligatured  in  two  places  and 
the  intermediate  portion  was  exsected.  A  fistula  was  then 
made  into  the  fundus  of  the  gall-bladder,  which  was  kept 
open.  The  animal  ate  well  on  the  day  of  the  operation, 
and  there  was  very  little  peritonitis.  The  only  observation 
in  which  contrary  results  were  obtained  is  one  made  by 
Blondlot.*  In  this  case  a  fistula  was  made  into  the  gall- 
bladder after  the  bile-duct  had  been  divided.     The  animal 


*  Blondlot,  "  Essai  sur  les  fonctions  du  foie  et  de  ses  annexes,"  Paris,  1840, 
p.  55  et  seq.  ;  and  "  Inutilite  de  la  bile  dans  la  digestion,"  Paris,  1851. 


242       EXCRETORY    FUNCTION    OF    THE    LIVER 

lived  for  five  years,  and  after  fifteen  days  following  the 
operation,  was  in  good  flesh  and  apparently  suffered  no 
inconvenience  from  the  discharge  of  the  bile  from  the 
fistula.  During  the  first  fifteen  days  the  animal  licked  the 
bile  from  the  fistula,  but  this  was  afterward  prevented  by 
a  muzzle.  After  a  time  he  made  no  attempt  to  lick  the 
bile.  Blondlot  attributed  the  emaciation  which  occurred 
during  the  first  fifteen  days  to  this  licking  of  the  bile. 
When  the  animal  died,  more  than  five  years  after  the  oper- 
ation, an  examination  of  the  parts  was  made  in  the  pres- 
ence of  several  physicians  and  students  of  medicine  and 
no  communication  could  be  found  between  the  bile-duct 
and  the  intestine.  From  this  observation  Blondlot  con- 
cluded that  the  bile  had  no  function  in  digestion  and  that 
it  was  a  purely  excrementitious  fluid;  and  he  assumed  that 
the  cause  of  death  in  other  experiments  of  a  similar  kind 
was  the  licking  of  the  bile  as  it  flowed  from  the  fistula. 
In  my  own  case  of  biliary  fistula,  in  which  the  dog  died 
after  thirty-eight  days,  the  animal  was  prevented  by  a  muz- 
zle from  licking  the  bile. 

The  only  point  to  consider,  as  it  seems  to  me,  in  this 
single  experiment  of  Blondlot,  is  whether  or  not  a  com- 
munication had  been  reestablished  between  the  bile-duct 
and  the  intestine.  If  such  a  communication  existed,  it 
would  be  easy  to  explain  the  survival  of  the  animal.  The 
following  experiment,  which  I  undertook  for  a  different 
purpose,  satisfied  me  upon  this  point: 

I  attempted  to  estimate  in  a  dog  the  entire  quantity 
of  bile  discharged  in  the  twentv-four  hours.  With  this 
object  in  view,  I  cut  down  upon  the  bile-duct,  emptied  the 
gall-bladder,  secured  a  canula  in  the  duct  and  attached  a 
rubber-bag  to  the  canula  for  the  purpose  of  collecting  the 
bile.  Twenty-three  hours  after  the  operation  the  bag  was 
in  place  and  nearly  full  of  bile.  Just  before  the  end  of  the 
twenty-four  hours,  however,  the  animal  ruptured  the  bag, 
and  the  experiment,  so  far  as  its  original  object  was  con- 
cerned, was  a  failure.  I  then  simply  pulled  the  canula  from 
the  wound  and  set  the  animal  at  liberty.  In  about  four 
weeks,  after  the  wound  had  closed  and  the  feces  had  be- 
come of  normal  color,  the  animal,  when  in  a  perfectly 
normal  condition,  was  killed  and  the  parts  were  carefully 
examined  in  the  presence  of  several  assistants.     It  is  well 


EXCRETORY    FUNCTION    OF   THE    LIVER       243 

known  that  in  dogs  ducts  that  have  been  divided  have  a 
remarkable  tendency  to  become  reestabHshed.  In  this 
case,  inasmuch  as  no  bile  was  discharged  externally  and 
the  feces  were  of  normal  color,  it  was  certain  that  the 
bile  was  discharged  into  the  intestine.  Nevertheless  I 
searched  for  more  than  an  hour  for  the  communication 
before  it  was  discovered.  The  only  reasonable  way,  as  it 
appears  to  me,  to  reconcile  the  single  experiment  of  Blond- 
lot  with  those  of  other  observers  is  to  suppose  that  in 
his  observation  a  communication  between  the  bile-duct 
and  the  intestine  had  become  established,  which  he  failed 
to  find.  The  difficulty  which  I  experienced  in  finding  the 
communication  in  my  own  observation  led  me  to  conclude 
that  a  communication  existed  in  the  case  reported  by 
Blondlot.  which  he  did  not  discover. 

It  is  in  accordance  with  my  own  observations,  as  well 
as  with  those  of  other  physiologists,  to  conclude  that  the 
bile  is  a  secretion,  and  that  it  has  a  function  to  perform 
in  connection  with  the  digestive  process,  which  function 
is  essential  to  life. 

Assuming  that  the  bile  has  an  important  and  an  essen- 
tial office  in  digestion,  is  it  not  possible  that  it  may  also 
serve  the  purpose  of  elimination,  and  contain  elements  of 
excretion!  This  is  a  view  which  has  not  been  advanced 
by  physiologists,  who  have  regarded  the  bile  either  as  a 
secretion  or  an  excretion  and  have  not  imagined  that  it 
could  serve  both  functions.  Before  I  take  up  the  experi- 
mental facts  bearing  upon  this  question.  I  propose  to  con- 
sider the  arguments  to  be  drawn  from  a  study  of  the  com- 
position of  the  bile  and  its  discharge  into  the  intestine. 
It  was  this  idea  which  first  led  me  to  investigate  the  physi- 
ological relations  of  cholesterin. 

The  bile  certainly  has  an  important  function  as  a  se- 
cretion; and  its  flow,  although  not  intermittent,  is  more 
abundant  during  the  process  of  intestinal  digestion.  The 
peculiar  biliary  salts,  the  glycocholate  and  the  taurocho- 
late  of  soda,  are  formed  in  the  liver  and  do  not  preexist 
in  the  blood.  When  the  structure  of  the  liver  is  invaded 
by  disease  so  as  to  interfere  with  the  production  of  bile, 
the  biliary  salts  do  not  accumulate  in  the  blood.  The  bil- 
iary salts  are  reabsorbed  in  a  modified  form  in  the  intestine; 
for  the  quantity  of  one  of  their  elements  (sulphur)  found 


244       EXCRETORY    FUNCTION    OF  THE    LIVER 

in  the  feces  is  very  much  less  than  the  quantity  discharged 
into  the  intestine. 

On  the  other  hand,  in  regard  to  one  constant  con- 
stituent of  the  ]n\e  (cholesterin),  it  is  not  known  to  have 
any  function  in  connection  with  digestion.  The  secretion 
of  bile  is  continuous,  although  its  flow  is  increased  during 
digestion.  Cholesterin,  while  it  is  an  invariable  constitu- 
ent of  the  bile,  exists  in  the  blood  and  in  certain  of  the 
tissues  of  the  body. 

The  questions  to  determine  experimentally  in  regard 
to  cholesterin  are  the  following: 

Is  cholesterin  produced  in  any  of  the  tissues  of  the 
body? 

Is  cholesterin  separated  from  the  blood  by  the  liver? 

When  the  liver  undergoes  structural  change  in  disease, 
does  cholesterin  accumulate  in  the  blood? 

Is  cholesterin  reabsorbed  in  the  intestine  or  is  it  dis- 
charged, either  unchanged  or  in  a  modified  form,  in  the 
feces? 

These  are  the  questions  which  I  endeavored  to  answer 
by  a  series  of  experimental  investigations,  made  in  the 
spring  of  1862,  and  published  in  October  of  the  same  year, 
in  the  "  American  Journal  of  the  Medical  Sciences." 

Process  for  the  Estimation  of  Cholesterin  in 
THE  Blood. — The  following  is  the  process  which  I  fixed 
upon,  after  a  num1)er  of  trials,  for  the  quantitative  analysis 
of  the  blood  for  cholesterin:  The  entire  blood,  serum  and 
clot,  is  evaporated  to  dryness.  The  dry  residue  is  then 
pulverized  in  an  agate  mortar  and  treated  for  tw-elve  to 
twenty-four  hours  with  ether,  in  the  proportion  of  about 
one  fluidounce  of  ether  to  one  hundred  grains  of  the  orig- 
inal w-eight  of  blood.  This  is  filtered,  and  the  ethereal  ex- 
tract, which  contains  cholesterin  and  fats,  is  evaporated. 
The  residue  of  this  evaporation  is  then  extracted  with  boil- 
ing alcohol,  in  the  proportion  of  one  fluidrachm  for  one 
hundred  grains  of  the  original  w^eight  of  blood.  This  ex- 
tract is  filtered  while  hot  and  the  filtrate  is  evaporated, 
leaving  the  cholesterin  and  a  certain  quantity  of  saponi- 
fiable  fats.  To  remove  the  saponifiable  fats,  add  to  the 
residue  a  weak  solution  of  potash,  and  allow  it  to  remain 
for  about  two  hours;  then  dilute  with  water,   filter,  and 


EXCRETORY   FUNCTION    OF  THE    LIVER       245 

wash  the  filter  with  water  until  the  liquid  which  passes 
through  becomes  neutral.  Dry  the  filter;  wash  it  with 
ether;  evaporate  the  ether;  extract  the  residue  with  hot  al- 
cohol as  before;  evaporate  the  alcoholic  extract,  and  the 
residue  will  consist  of  cholesterin,  perfectly  pure,  as  can 
be  determined  by  means  of  the  microscope.  Using  this 
process  for  the  determination  of  cholesterin,  a  number  of 
observations  were  made  upon  dogs,  from  which  I  select 
the  following  as  typical,  the  results  having  been  repeat- 
edly confirmed: 

Observation  I.  Experiment  showing  an  Increase  in  Choles- 
terin IN  the  Blood  passing  through  the  Brain.  (The  dog 
was  not  etherized.) 

Blood  from  the  carotid,  140.847  grains,  contained  0.108  grain 
of  cholesterin,  or  0.768  part  of  cholesterin  per  1,000. 

Blood  from  the  internal  jugular,  97.811  grains,  contained  0.092 
grain  of  cholesterin,  or  0.947  part  of  cholesterin  per  1,000. 

The  increase  in  the  proportion  of  cholesterin  in  the  blood  in 
pasing  through  the  brain  was  23.309  per  cent. 

This  observation,  which  was  frequently  repeated  with 
the  same  general  result,  seems  to  show  that  the  blood 
gains  cholesterin  in  its  passage  through  the  brain.  It  is 
well  known  that  cholesterin  is  always  present  in  nervous 
substance,  not  in  a  crystallized  form,  but  in  a  condition  of 
molecular  union  with  nitrogenous  and  other  matters.  In 
order  to  verify  this  fact,  I  examined  the  brains  of  two  sub- 
jects who  had  been  killed  instantly  by  accident  while  in 
perfect  health,  in  one  case  finding  a  proportion  of  choles- 
terin of  7.729  parts  per  1,000,  and  in  the  other,  11.456 
parts  per  i  ,000. 

The  experiment  just  described  was  made  with  a  view 
of  determining  whether  or  not  the  brain  gives  up  choles- 
terin to  the  blood  as  it  circulates  through  this  organ;  and 
the  following  experiment  was  made  to  determine  whether 
the  venous  blood  of  other  parts  contains  an  excess  of  cho- 
lesterin. Theoretically,  the  blood  of  the  femoral  vein 
should  contain  a  little  more  cholesterin  than  arterial  blood, 
this  excess  being  derived  from  the  nerves  of  the  extremity, 
although  the  increase  would  probably  be  not  so  great  as 
in  the  blood  of  the  internal  jugular,  which  comes  almost 
exclusively  from  the  great  nervous  centre. 


246       EXCRETORY    FUNCTION    OF  THE    LIVER 
Observation  II.     Experiment  showing  an  Excess  of  Choles- 

TERIN    IN   THE   BlOOD  OF  THE   INTERNAL  JUGULAR  AND   FeMORAL 

Veins  over  the  Arterial  Blood.     (The  dog  was  not  ether- 
ized.) 

Blood  from  the  carotid,  143.625  grains,  contained  0.679  grain 
of  cholesterin,  or  0.967  part  of  cholesterin  per  1,000. 

Blood  from  the  internal  jugular,  29.956  grains,  contained  0.046 
grain  of  cholesterin,  or  1.545  part  per  1,000. 

Blood  from  the  femoral  vein,  45.035  grains,  contained  0.046 
grain  of  cholesterin,  or  1.028  part  per  1,000. 

The  increase  in  the  pro|)ortion  of  cholesterin  in  the  blood  in 
passing  through  the  brain  was  59.772  per  cent. 

The  increase  in  the  proportion  of  cholesterin  in  the  blood  in 
passing  through  the  lower  extremity  was  6.308  per  cent. 

Thi.s  experiment  confirms  the  previous  observation 
upon  the  increase  of  cholesterin  in  the  blood  in  passing 
through  the  brain,  and  it  shows,  in  addition,  that  the 
blood  gains  cholesterin  in  other  parts.  Inasmuch  as  the 
nervous  tissue  is  the  only  tissue  in  the  extremities  which 
contains  cholesterin.  it  is  probable  that  the  excess  con- 
tained in  the  blood  of  the  femoral  vein  over  the  arterial 
blood  was  derived  from  the  nerves. 

It  occurred  to  me  that  cases  of  old  hemiplegia  would 
present  favorable  conditions  for  verifying  in  the  human 
subject  the  observations  made  on  the  lower  animals.  It 
has  been  ascertained  that  when  the  function  of  nerves 
is  permanently  abolished  they  soon  become  degenerated 
and  their  nutrition  is  modified;  and  it  seems  probable  that 
if  cholesterin  is  one  of  their  important  products  of  dis- 
assimilation,  the  quantity  of  cholesterin  in  the  blood  from 
paralyzed  parts  should  be  very  small.  Taking  the  blood, 
for  example,  from  the  paralyzed  arm  of  a  hemiplegic,  this 
blood,  coming  from  paralyzed  parts,  should  contain  less 
cholesterin  than  the  blood  from  the  sound  arm.  Of  course, 
the  blood  from  the  arm  contains  no  blood  which  has  passed 
through  the  brain,  which  is  assumed  to  be  sound  upon  the 
paralyzed  side.  I  examined,  therefore,  the  blood  from  both 
arms  in  three  cases  of  hemiplegia  in  the  Charity  Hospital 
on  Blackwell's  Island: 

Case  I. — Sarah  Rumsby,  set.  47,  is  affected  with  hemiplegia  of 
the  left  side.  Two  years  ago  she  was  taken  with  apoplexy  and  was 
insensible  for  three  days.  When  she  recovered  consciousness  she 
found  herself  paralyzed  on  the  left  side.  She  says  she  had  epilepsy 
four  or  five  years  before  the  attack  of  apoplexy.     She  has  now 


EXCRETORY    FUNCTION    OF  THE    LIVER       247 


complete  paralysis  of  motion  on  the  affected  side,  with  the  excep- 
tion of  some  slight  power  over  the  fingers.  Sensation  is  not  af- 
fected.    The  speech  is  perfect  and  her  general  health  is  good. 

Case  II. — Anna  Wilson,  aet.  23,  is  affected  with  hemiplegia  of 
the  right  side.  Four  months  ago  she  became  unconscious  and  re- 
covered in  one  day,  with  loss  of  motion  and  sensation  on  the  right 
side.  She  is  now  improving  and  can  use  the  right  arm  slightly. 
The  leg  is  not  so  much  improved  because  she  will  make  no  eft'ort 
to  use  it. 

Case  III. — Honora  Sullivan,  set.  40,  is  affected  with  hemiplegia 
of  the  right  side.  About  six  months  ago  she  became  unconscious, 
recovering  the  next  day,  with  paralysis.  The  leg  was  less  affected 
than  the  arm  from  the  first.  Her  condition  is  about  stationary  as 
regards  the  arm-  but  the  leg  has  somewhat  improved. 

A  small  quantity  of  blood  was  drawn  from  either  arm 
in  these  three  cases.  In  each  instance  it  was  drawn  from 
the  paralyzed  side  with  difficulty  and  btit  a  small  qtiantity 
could  be  obtained. 

The  specimens  were  all  examined  for  cholesterin,  with 
the  following  results: 

Observation  III.     Quantities  of  Cholesterin  in  the  Blood  of  the 
Paralyzed  and  the  Sound  Sides  in  Three  Cases  of  Hemiplegia 


Cases. 

Blood. 

Cholesterin. 

Cholesterin  per  i,ooo  parts. 

Case      I. 

Paralyzed  side. . . . 

Sound  side 

Paralyzed  side.  .  .  . 

Sound  side 

Paralyzed  side. . .  . 
Sound  side 

grains. 
55-458 

128.407 
18.381 
66.396 
21.842 
52.261 

grains. 

The  watch-glass  contained 
0.031  grain  of  substance, 
but  the  most  careful  ex- 
amination with  the  mi- 
croscope failed  to  show 
crystals  of  cholesterin. 

0.481. 

Same  as  in  Case  I. 

Case    II 

0.062 

Case  III 

0.062 

0.808. 

Same  as  in  Case  I. 

0.031 

0,579. 

The  conclusion  from  the  experiments  upon  dogs  and 
the  three  observations  upon  the  human  subject  is  inevita- 
ble, that  cholesterin  is  produced  in  the  substance  of  the 
brain  and  in  the  nervous  tissue  generally,  as  this  substance 
is  not  contained  in  the  mitscular  tissue  or  in  any  other 
parts  except  the  crystalline  lens,  the  liver  and  the  spleen. 
The  question  now  to  determine  is  the  relation  of  choles- 
terin to  the  nervous  system.  Is  it  one  of  the  products  of 
disassimilation  of  its  tissue?  If  this  is  the  fact,  choles- 
terin is  an  excrementitious  product  and  it  must  be  sepa- 


248       EXCRETORY    FUNCTION    OF   THE    LIVER 

rated  from  the  blood  by  some  organ  or  organs  and  dis- 
charged from  the  body.  Inasmuch  as  the  bile  always  con- 
tains cholesterin,  we  naturally  look  to  the  liver  as  the 
organ  for  its  elimination;  for  it  is  not  found  in  the  secre- 
tion of  any  other  gland. 

1  employed  essentially  the  same  method  in  studying 
the  (juestion  of  the  elimination  of  cholesterin  as  that  used 
in  determining  the  seat  of  its  production,  analyzing  the 
blood  going  to  and  coming  from  the  liver.  Upon  this 
point  I  made  a  number  of  observations,  the  general  results 
of  which  were  invariable.  The  following  experiment  is  a 
type  of  these  observations: 

Observation   IV.     Experiment  showing  that  Cholesterin   is 

SEPARATED    FROM     THE     BlOOD     IN     ITS     PASSAGE    THROUGH     THE 

Liver.     (The  dog  was  etherized.) 

Arterial  blood,  159.537  grains,  contained  0.200  grain  of  choles- 
terin, or  1.257  P'li't  of  cholesterin  per  1,000. 

Blood  of  portal  vein,  168.257  grains,  contained  0.170  grain  of 
cholesterin,  or  1.009  P'^''^  of  cholesterin  per  1,000. 

Blood  of  hepatic  vein,  79.848  grains,  contained  0.077  grain  of 
cholesterin,  or  0.964  part  of  cholesterin  per  1,000. 

The  loss  in  the  proportion  of  cholesterin  in  arterial  blood  in 
passing  through  the  liver  was  23.309  per  cent. 

The  loss  in  the  proportion  of  cholesterin  in  the  portal  blood  in 
passing  through  the  liver  was  4.460  per  cent. 

The  bile  always  contains  a  certain  proportion  of  cho- 
lesterin, which  I  found,  in  a  specimen  taken  from  the  gall- 
bladder of  a  subject  who  had  been  killed  instantly  wdiile 
in  perfect  health,  to  be  0.618  part  per  1,000.  As  I  have 
demonstrated  that  the  blood  gains  cholesterin  in  its  pas- 
sage through  the  brain  and  probably  also  from  the  gen- 
eral nervous  tissue,  that  cholesterin  is  separated  from  the 
blood  in  its  passage  through  the  liver,  and  that  cholesterin 
is  invariably  found  in  the  bile  and  is  discharged  into  the 
intestine,  it  seems  to  be  proved  that  one  of  the  functions 
of  the  liver  is  to  eliminate  this  substance.  If  it  can  be 
shown  that  the  cholesterin  thus  separated  from  the  blood 
by  the  liver  is  discharged  from  the  body,  the  fact  that  it 
is  apparently  produced  in  the  nervous  tissue  and  is  taken 
up  by  the  blood  would  point  strongly  to  the  conclusion 
that  cholesterin  is  an  excrementitious  matter  and  is 
one  of  the  products  of  disassimilation  of  the  nervous 
tissue. 


EXCRETORY    FUNCTION    OF  THE    LIVER       249 


Stercorin. — I  made  repeated  examinations  of  the  nor- 
mal feces,  with  the  view  of  determining  the  presence  of  cho- 
lesterin  and  its  quantity.  Although  it  is  often  stated  by 
authors  that  cholesterin  exists  in  the  feces,  I  was  unable 
to  find  it  after  the  most  careful  examination;  and  I  subse- 
quently failed  to  discover  any  writer  who  had  actually  ex- 
tracted it  from  the  normal  dejections.  The  process  Vvhich 
I  employed  was  essentially  the  same  as  that  used  in  exam- 
inations of  the  blood,  except  that  the  extracts  were  de- 
colorized by  filtering  through  animal  charcoal,  and  the 
alcoholic  extract  was  treated  with  potash  for  one  or  two 
liours  at  nearly  the  boiling  point.  Treated  in  this  way, 
the  feces  gave  an  extract  which  was  non-saponifiable  but 
which  did  not  crystallize  for  several  days.  After  a  few 
days,  delicate,  needle-shaped  crystals  began  to  appear, 
gradually  increasing  in  number  and  breadth,  and  as  they 
became  broader,  becoming  split  at  the  points  and  edges. 
These  crystals  presented  all  the  characters  of  the  crystals 
of  a  substance  extracted  from  the  serum  of  the  blood 
by  Boudet,  in  1833  ("  /\nnales  de  chimie  et  de  physique  "), 
which  he  called  "  seroline."  In  some  of  my  earlier  ob- 
servations upon  the 
blood,  I  obtained  these 
■crystals;  but  I  came  to 
the  conclusion  that  the 
so-called  seroline  was 
not  a  normal  constitu- 
ent of  the  blood  but 
Avas  formed  during  the 
process  used  for  the 
•extraction  of  choles- 
terin. With  this  view, 
finding  the  so-called 
seroline  to  be  a  con- 
stant constituent  of 
the  normal  feces,  I 
called  the  substance 
stercorin,  regarding  it 
as  one  of  the  excre- 
mentitious  constituents  of  fecal  matter.  Crystals  of  ster- 
corin are  shown  in  the  accompanying  figure.  The  round- 
ed drops  probably  are  composed  of  the  same  substance,  as 
17 


Stercorin  from  normal  human  feces  (-,%  inch 
objective). 


250       EXCRETORY    FUNCTION    OF   THE    LIVER 

they  disappear  when  the  crystallization  is  complete.  The 
idea  that  these  crystals  obtained  from  blood  result  from 
the  transformation  of  cholesterin  is  strengthened  by  the 
tact  that  the  cholesterin  of  the  bile  is  changed  into  ster- 
corin  in  its  passage  through  the  alimentary  canal.  Sterco- 
rin,  like  cholesterin,  is  soluble  in  ether,  very  soluble  in  hot 
alcohol  and  strikes  a  red  color  with  strong  sulphuric  acid. 

I  obtained  from  the  feces  of  the  twenty-four  hours  of 
a  perfectly  healthy  man  10.417  grains  of  stercorin.  It  is 
estimated  by  Dalton  that  the  total  quantity  of  bile  in  twen- 
ty-four hours  is  16,940.00  grains,  and  the  total  quantity 
of  cholesterin,  according  to  my  estimate  of  0.618  parts 
per  1,000,  is  10.469  grains,  giving  a  difference  between  the 
estimated  quantity  of  cholesterin  and  the  actual  quantity 
of  stercorin  extracted  from  the  feces  of  only  0.052  of  a 
grain.  This  sustains  the  idea  of  the  change  of  the  choles- 
terin of  the  bile  into  the  stercorin  of  the  feces. 

Observations  made  by  myself  and  others  seem  to  show 
that  the  change  of  cholesterin  into  stercorin  is  incidental 
to  the  process  of  digestion.  Cholesterin  is  found  in  quan- 
tity in  the  feces  of  hibernating  animals  and  in  the  meco- 
nium, when,  of  course,  there  is  no  intestinal  digestion,  but 
when  the  bile  is  none  the  less  discharged  into  the  alimen- 
tary canal.  I  made  an  examination  of  human  meconium 
and  found  cholesterin  in  the  proportion  of  6.245  parts  per 
1,000  and  no  stercorin.  I  examined  the  human  feces  in 
a  case  of  simple  jaundice  from  obstruction  of  the  bile-duct, 
the  feces  being  clay-colored,  and  found  neither  cholesterin 
nor  stercorin.  Nineteen  days  after,  w'hen  the  jaundice  had 
disappeared  and  the  color  of  the  feces  was  normal,  I  found 
stercorin  and  no  cholesterin.  In  the  feces  of  a  dog  which 
had  been  deprived  of  food  for  forty-eight  hours.  I  found 
stercorin  and  a  small  quantity  of  cholesterin.  So  far  as 
can  be  learned  from  these  facts  and  observations,  then,  it 
seems  that  the  cholesterin  of  the  bile  is  discharged  in  the 
feces  unchanged  when  no  digestion  takes  place,  but  that 
it  is  discharged  in  the  form  of  stercorin  under  the  ordinary 
and  normal  conditions  of  the  digestive  process. 

Pathological  Relations  of  Cholesterin. — Cho- 
LESTEREMiA. — A  knowledge  of  the  relations  of  urea  to  nu- 
•trition  bears  so  directly  upon  the  pathology  of  renal  dis- 


EXCRETORY    FUNCTION    OF  THE    LIVER       251 

eases,  that  the  pathological  relations  of  any  newly-discov- 
ered excrementitious  matter  assumes  at  once  the  greatest 
importance.  If  it  is  true  that  cholesterin,  like  urea,  is  a 
product  of  disassimilation,  and  that  it  is  eHminated  by  the 
liver  as  urea  is  eliminated  by  the  kidneys,  one  would  ex- 
pect to  find,  in  cases  of  serious  structural  disease  of  the 
liver,  an  accumulation  of  cholesterin  in  the  blood,  or  cho- 
lesteremia,  as  uremia  exists  in  certain  stages  of  extensive 
organic  disease  of  the  kidneys.  It  has  long  been  observed, 
indeed,  that  although  simple  jaundice  due  to  resorption 
of  the  coloring  matter  of  the  bile  usually  is  a  trivial  affec- 
tion, there  are  cases  of  extensive  change  in  the  structure 
of  the  liver  in  which  there  is  apparently  a  toxic  condition 
dependent  upon  the  presence  of  some  excrementitious  or 
poisonous  substance  in  the  blood.  Pathologists  have  ex- 
amined the  blood  in  such  cases  wdth  the  view  of  ascertain- 
ing the  nature  of  the  supposed  poisonous  matter.  Frerichs 
and  others  repeatedly  examined  the  blood  in  cases  of  grave 
jaundice,  expecting  to  discover  the  biliary  salts  or  acids, 
but  they  never  detected  any  substance  which  would  react 
with  Pettenkofers  test.*  Becquerel  and  Rodier  exam- 
ined the  blood  in  a  case  of  jaundice  and  found  "  cholesterin 
excessively  abundant,"  but  they  did  not  recognize  the  sig- 
nificance of  this  fact.t  In  such  cases  pathologists  have 
looked  for  the  bihary  acids  and  their  derivatives  and  not 
for  cholesterin.  In  order  to  throw  some  light  upon  the 
pathology  of  grave  jaundice,  Muller,:|:  Kunde,*  Lehmann,|| 
and  Moleschott  ^  have  extirpated  the  liver  in  frogs  and 
kept  the  animals  alive  for  several  days,  or  even  two  or 
three  weeks.  On  examining  the  blood,  these  physiologists 
failed  to  discover  the  biliary  salts.  They  made  no  analyses 
of  the  blood  for  cholesterin.  I  hope  to  be  able  to  show^ 
conclusively,  by  observations  upon  cases  of  disease  of  the 
liver  in  the  human  subject,  that  there  may  be  an  accumu- 
lation of  cholesterin  in  the  blood,  or  cholesteremia,  and 
that  this  occurs  in  certain  cases  of  serious  structural  dis- 
ease of  the  liver. 


*  Frerichs,  "Diseases  of  the  Liver,"  London,  1S60,  vol.  i.,  p.  95- 

+  Becquerel  et  Rodier,  "Traite  de  chimie  pathologique,"  Paris,  1854,  p.  210. 
X  Miiller,  "  Manuel  de  physiologie,"  Paris,  1851,  tome  i.,  p.  122. 

*  Kunde,  "  De  Hepatis  Extirpatione,"  Berolini,  1850. 

II  Lehmann,  "  Physiological  Chemistry,"  Philadelphia,  1855,  vol.  i.,  p.  476 
^  Moleschott,  "  Comptes  rendus,"  Paris,  1855,  tome  xl.,  p.  1040. 


252       EXCRETORY    FUNCTION    OF    THE    LIVER 

In  cases  of  simple  jaundice  there  is  resorption  of  the 
coloring  matter  of  the  bile  from  the  excretory  passages. 

In  cases  of  grave  jaundice,  which  almost  invariably  ter- 
minate fatally,  there  is  cholesteremia,  or  accumulation  of 
cholesterin  in  the  blood. 

There  are  cases  of  structural  disease  of  the  liver  in 
which  there  is  no  jaundice,  but  nevertheless  there  is  cho- 
lesteremia. 

In  the  following  cases,  having  first  determined  the  pro- 
portion of  cholesterin  in  normal  blood,  I  examined  the 
blood  for  cholesterin  with  'reference  to  the  points  just 
stated: 

Observation  V.  Proportion  of  Cholesterin  in  Normal 
Blood. — 

Male,  ast.  35    0-445  part  of  cholesterin  per  i  ,000. 

"       "    22   0.658         "  "  " 

"    24   0.751 

Observation  VI.  Case  of  Jaundice  Dependent  probably 
UPON  Duodenitis. — This  case  presented  the  symptoms  of  simple 
jaundice  from  temporary  obstruction  of  the  bile-duct.  June  21, 
1862,  212.428  grains  of  blood  were  taken  from  the  arm.  The  pro- 
portion of  cholesterin  per  1,000  was  0.508,  which  is  within  the 
limits  of  health,  according  to  the  results  obtained  in  my  examina- 
tions of  normal  blood.  The  feces,  which  were  clay-colored,  were 
examined,  and  I  found  neither  cholesterin  nor  stercorin.  July  11, 
the  patient  had  entirely  recovered;  there  was  no  jaundice,  and  the 
feces  had  become  normal. 

Observation  VII.  Case  of  Grave  Jaundice  with  Cirrhosis. 
— This  case  presented  intense  jaundice,  ascites,  great  general  pros- 
tration, and  toward  the  close  of  life,  symptoms  of  blood-poisoning. 
The  patient  was  admitted  to  the  Charity  Hospital  on  Blackwell's 
Island,  June  16,  1862.  On  June  21  50.776  grains  of  blood  were 
taken  from  the  arm.  This  blood  contained  a  proportion  of  1.850 
part  of  cholesterin  per  1,000,  an  increase  of  146.338  per  cent,  over 
the  maximum  quantity  obtained  from  normal  blood.  The  patient 
died  June  27,  1862.  There  was  double  vision  six  days  before  death 
and  stupor  for  the  last  three  or  four  days.  The  liver,  examined 
after  death,  was  in  a  condition  of  cirrhosis.  The  gall-bladder  was 
contracted  and  contained  but  about  two  drachms  of  bile.  The 
fibrous  substance  of  the  liver  was  increased  in  quantity  and  the 
liver-cells  were  shrunken.  The  feces  were  taken  a  few  days  before 
death.  The  amount  was  small,  only  272.1  grains  in  twenty-four 
hours,  and  contained  0.077  of  ^  grain  of  stercorin.  I  found  10.417 
grains  of  stercorin  in  the  feces  of  the  twenty-four  hours  in  a 
healthy  male. 

Observation  VIII.  Case  of  Cirrhosis  with  Ascites  and 
Considerable  Affection  of  the  General  Health. — In  this  case 


EXCRETORY   FUNCTION    OF  THE    LIVER       253 

there  was  general  prostration  confining  the  patient  to  the  bed. 
After  a  tapping,  the  hver  was  explored  and  found  to  be  consider- 
ably diminished  in  size;  1 17.193  grains  of  blood  were  taken  from 
the  arm,  containing  a  proportion  of  0.922  of  a  part  of  cholesterin 
per  1,000,  an  increase  of  22.769  per  cent,  over  the  maximum  pro- 
portion obtained  in  my  examinations  of  normal  blood.  In  this  case 
there  were  no  nervous  symptoms. 

Observation  IX.  Case  of  Cirrhosis  with  Ascites  and 
Slight  Constitutional  Disturbance. — This  patient  had  suffered 
from  ascites  for  eighteen  months  and  had  been  tapped  about  thirty 
times.  He  is  immediately  relieved  by  tapping  and  goes  out  the 
next  day.  July  i,  1862,  251.567  grains  of  blood  were  taken  from 
the  arm,  which  gave  a  proportion  of  cholesterin  of  0.246  of  a  part 
per  1,000,  or  44.719  per  cent,  less  than  the  minimum  obtained  in 
my  examinations  of  normal  blood. 

The  cases  just  detailed,  taken  in  connection  with  my 
observations  upon  animals,  are  certainly  very  striking.  In 
the  case  of  simple  jaundice,  which  recovered,  the  propor- 
tion of  cholesterin  in  the  blood  was  within  the  limits  of 
health.  In  the  case  of  ascites,  the  patient  not  suffering 
much  disturbance,  the  proportion  of  cholesterin  in  the 
blood  was  considerably  below  the  normal  standard.  In 
the  case  of  grave  jaundice,  which  terminated  fatally  with 
symptoms  of  serious  disturbance  of  the  nervous  system, 
the  proportion  of  cholesterin  in  the  blood  was  enormously 
increased,  being  nearly  three  times  greater  than  the  maxi- 
mum obtained  in  my  examinations  of  normal  blood.  In 
the  case  of  cirrhosis  with  considerable  affection  of  the  gen- 
eral health,  the  proportion  of  cholesterin  in  the  blood  was 
considerably  above  the  maximum  obtained  in  my  exam- 
inations of  normal  blood. 

Literature  bearing  upon  the  "  New  Excretory  Function  of 
THE  Liver,"  since  the  Publication  of  my  Observations  in 
1862 

October,  1862. — j\Iy  researches  were  published  in  the  "  Ameri- 
can Journal  of  the  Medical  Sciences." 

1868. — A  translation  of  my  memoir  into  French  was  published 
in  Paris  and  presented  to  the  Academy  of  Sciences  for  the  Mon- 
thyon  prize. 

1869. — The  commission  from  the  French  Academy  of  Sciences 
reported  upon  my  observations  and  awarded  an  "  honorable  men- 
tion "  with  a  "  recompense  "  of  fifteen  hundred  francs. 

1869. — Grollemund  ("These  de  Strasbourg")  made  observa- 
tions upon  the  injection  of  the  biliary  salts  into  the  blood  in  large 
quantity  in  dogs,  and  noted  certain  disturbances  of  the  nervous 
system. 


254       EXCRETORY    FUNCTION    OF   THE    LIVER 

1869. — Tincclin  ("These  de  Strasbourg")  made  observations 
in  which  he  failed  to  obtain  any  marked  nervous  disturbances  fol- 
lowing the  injection  of  the  biliary  salts  into  the  blood  in  dogs. 

1869. — Pages  ("These  de  Strasbourg")  injected  the  bile-duct 
in  dogs  with  a  solution  of  sulphate  of  iron,  which  he  thought  de- 
stroyed the  epithelium  of  the  liver  and  interfered  with  its  elimina- 
tive  function,  producing  accumulation  of  cholesterin  in  the  blood. 

1870. — Feltz  and  Ritter  ("Journal  de  I'anatomie,"  Paris,  1870) 
confirmed  the  results  obtained  by  Pages  with  the  sulphate  of  iron. 
They  found  no  marked  effects  following  the  injection  of  the  biliary 
salts,  taurin  or  glycochol  into  the  veins.  They  also  injected  cho- 
lesterin in  soap  and  water.  The  cholesterin  was  not  dissolved,  and 
masses  of  cholesterin  were  found  in  the  small  pulmonary  vessels, 
producing  death  by  embolism. 

1872. — Picot  ("Journal  de  Tanatomie,"  Paris,  1872)  noted  an 
accumulation  of  cholesterin  in  the  blood  in  a  case  of  acute  yellow 
atrophy  of  the  liver  which  terminated  fatally.  He  found  a  pro- 
portion of  cholesterin  in  the  blood  in  this  case  of  1.804  P^^t  per 
1,000,  more  than  double  the  maximum  which  I  obtained  in  exam- 
inations of  normal  blood. 

1873.— Koloman  Miiller  ("  Archiv  fiir  experimentelle  Patholo- 
gic und  Pharmakologie,"  Leipzig,  1873)  made  an  elaborate  series 
of  experiments  upon  dogs.  No  serious  or  marked  results  followed 
the  injection  of  the  biliary  salts  or  taurin  into  the  blood.  He 
rubbed  cholesterin  with  glycerin  and  made  a  solution  in  soap  and 
water.  He  injected  2.16  fiuidounces  of  this  solution,  containing 
about  69  grains  of  cholesterin,  into  the  veins.  In  five  experiments 
he  produced  "  a  complete  picture  of  the  symptoms  of  grave  jaun- 
dice." 

Conclusions  of  Koloman  Muller. — "  It  appears  to  me  to  be 
certain  that  those  cerebral  symptoms  which  accompany  severe  jaun- 
dice and  many  diseases  of  the  liver,  the  general  manifestations  of 
which  have  been  called  '  cholemic  intoxication,'  are  produced  by 
an  abnormal  accumulation  of  cholesterin  in  the  blood.  This  accu- 
mulation of  cholesterin  is  contingent  upon  that  alteration  of  the 
tissue  of  the  liver,  which,  in  such  cases,  it  suffers  more  or  less." 

1875  and  1876. — Feltz  and  Ritter  ("Journal  de  I'anatomie," 
Paris,  1875  and  1876)  in  opposition  to  their  former  experiments, 
conclude  that  the  biliary  salts  injected  into  the  blood  produce  grave 
changes,  mainly  in  the  blood  corpuscles.  The  corpuscles  become 
diffluent,  change  their  form,  the  hemoglobin  transudes  and  crystal- 
lizes, and  the  power  of  absorption  of  oxygen  progressively  dimin- 
ishes. 

The  general  results  of  observations  bearing  upon  the 
physiological  relations  of  cholesterin,  made  since  1862,  are 
confirmatory  of  my  observations.  As  regards  cholestere- 
mia.  the  experiments  of  Muller  are  the  most  important. 
Indeed,  they  supply  the  only  missing  link  in  my  chain  of 
experimental  evidence;  and  they  show  conclusively  that  the 


EXCRETORY    FUNCTION    OF  THE    LIVER       255 

symptoms  of  "  grave  jaundice,"  which  I  connected  with 
cholesteremia,  may  be  produced  by  the  artificial  introduc- 
tion of  cholesterin  into  the  circulation. 

As  an  inevitable  result  of  my  observations,  confirmed 
by  others  and  extended  by  Koloman  Miiller,  I  can  now 
confidently  repeat  the  conclusions  which  I  published  in 
1862. 

CONCLUSIONS 

I.  Cholesterin  exists  in  the  bile,  the  blood,  the  nervous 
matter,  the  crystalline  lens  and  the  meconium,  but  does 
not  exist  in  the  feces  under  ordinary  conditions.  The 
quantity  of  cholesterin  in  the  blood  of  the  arm  is  five  to 
eight  times  more  than  the  ordinary  estimate. 

II.  Cholesterin  is  formed,  in  great  part  if  not  entirely, 
in  the  substance  of  the  nervous  matter,  where  it  exists  in 
great  quantity  and  from  which  it  is  taken  up  by  the  blood 
and  constitutes  one  of  the  most  important  of  the  effete, 
or  excrementitious  products  of  the  body.  Its  formation 
is  constant  and  it  always  exists  in  the  nervous  matter  and 
the  circulating  fluid. 

III.  Cholesterin  is  separated  from  the  blood  by  the 
liver,  appears  as  a  constant  element  of  the  bile  and  is  dis- 
charged into  the  alimentary  canal.  The  history  of  this 
substance,  in  the  circulating  fluid  and  in  the  bile,  marks 
it  as  a  product  destined  to  be  discharged  from  the  body 
as  an  excretion.  It  preexists  in  the  blood,  subserves  no 
useful  purpose  in  the  economy,  is  separated  by  and  not 
formed  in  the  liver,  and  if  this  separation  is  interfered 
with,  it  accumulates  in  the  system. 

IV.  The  bile  has  two  separate  and  distinct  functions 
dependent  on  the  presence  of  two  constituents  of  entirely 
difTerent  characters.  It  has  a  function  connected  with 
nutrition.  This  is  dependent  on  the  presence  of  the  glyco- 
cholate  and  taurocholate  of  soda,  which  do  not  preexist 
in  the  blood,  subserve  a  useful  purpose  in  the  economy  and 
are  not  discharged  from  the  body,  are  found  in  the  liver 
and  peculiar  to  the  bile,  do  not  accumulate  in  the  blood 
w^hen  the  function  of  the  liver  is  interfered  with,  and  are, 
in  short,  products  of  secretion.  The  bile  has  another  func- 
tion connected  with  depuration,  which  is  dependent  on 
the  presence  of  cholesterin,  which  is  an  excretion.     The 


25.6       EXCRETORY    FUNCTION    OF   THE    LIVER 

ilovv  of  bile  is  rcmiltciit.  l)cini;  much  increased  during  the 
(hgestive  act,  but  produced  (hu-ing  the  intervals  of  diges- 
tion for  the  purpose  of  separating  cholesterin  from  the 
blood. 

V.  The  ordinary  normal  feces  do  not  contain  choles- 
terin but  contain  stercorin — formerly  called  "  seroline  " 
from  its  being  supposed  to  exist  only  in  the  serum  of  the 
blood.  Stercorin  results  from  a  transformation  of  the 
cholesterin  of  the  bile  during  the  digestive  act. 

VI.  The  change  of  cholesterin  into  stercorin  does  not 
take  place  when  digestion  is  arrested  or  before  this  pro- 
cess begins;  consequently  stercorin  is  not  found  in  the 
meconium  or  in  the  feces  of  hibernating  animals  during 
their  torpid  condition.  These  matters  contain  cholesterin 
in  large  abundance,  which  also  sometimes  appears  in  the 
feces  of  animals  after  a  prolonged  fast.  Stercorin  is  the 
form  in  w^hich  cholesterin  is  discharged  from  the  body. 

VII.  The  difference  between  the  two  familiar  varieties 
of  jaundice,  one  characterized  only  by  yellowness  of  the 
skin  and  comparatively  innocuous,  wdiile  the  other  is  at- 
tended with  very  grave  symptoms  and  is  almost  invari- 
ably fatal,  is  dependent  upon  the  obstruction  of  the  bile 
in  one  case,  and  its  suppression  in  the  other.  In  the  first 
instance,  the  bile  is  confined  in  the  excretory  passages  and 
its  coloring  matter  is  absorbed;  while  in  the  other,  choles- 
terin is  retained  in  the  blood. 

VIII.  There  is  a  condition  of  the  blood  dependent 
upon  the  accumulation  of  cholesterin,  which  I  have  called 
cholesteremia.  This  occurs  only  when  there  is  structural 
change  in  the  liver  which  incapacitates  it  from  performing 
its  excretory  function.  It  is  characterized  by  symptoms 
of  a  grave  character  referable  to  the  brain  and  probably 
is  dependent  upon  the  effects  of  the  retained  cholesterin 
on  this  organ.     This  occurs  with  or  without  jaundice. 

IX.  Cholesteremia  does  not  occur  in  every  instance 
of  structural  disease  of  the  liver.  Enough  of  the  liver 
must  be  destroyed  to  prevent  the  due  elimination  of  cho- 
lesterin. In  cases  in  which  the  organ  is  but  moderately 
afTected,  the  sound  portion  is  capable  of  performing  the 
eliminative  function  of  the  whole. 

X.  In  cases  of  simple  jaundice,  when  the  feces  are  de- 
colorized and  the  bile  is  entirely  shut  off  from  the  intestine^ 


EXCRETORY    FUNCTION    OF  THE    LIVER       257 

stercorin  is  not  found  in  the  evacuations;  but  in  cases  of 
jaundice  with  cholesteremia,  stercorin  may  be  found, 
though  always  very  much  diminished  in  quantity,  showmg 
that  there  is  an  insufficiency  in  the  separation  of  the  cho- 
lesterin  from  the  blood,  although  its  excretion  is  not  en- 
tirely suspended.  After  death,  but  a  small  quantity  of 
bile  is  found  in  the  gall-bladder. 


XI 

STERCORIN   AND   CHOLESTEREMIA  * 

Published  in  the  "  New  York  Medical  Journal "  for  June  5,   1S97. 

Looking  far  into  the  future,  it  seems  possible  that  our 
successors  may  fix  upon  the  month  of  May,  1946,  as  the 
true  centennial  of  the  American  Medical  Association,  dat- 
ing the  origin  of  this  body  from  May,  1846,  when  a  con- 
vention of  representatives  of  our  ])rofession,  held  in  New 
York,  proposed  the  formation  of  a  National  Association, 
which  was  formally  organized  in  1847.  If  your  orator 
of  to-day  finds  it  impossible  to  do  justice  to  this  occa- 
sion, how  much  more  difficult  will  it  be  to  present,  in  a 
single  address,  an  adequate  picture  of  a  full  century  of 
medical  progress!  The  year  1946  will  be  the  centennial 
of  the  application  of  anesthesia  to  surgery.  It  will  be 
the  third  jubilee  of  the  crowning  glory  of  the  eighteenth 
century,  the  completion  of  the  discovery  of  vaccination, 
when  the  terrible  scourge,  smallpox,  which  had  been  more 
destructive  to  human  life  than  war  or  famine,  w^as  virtually 
subdued.  At  the  Jenner  Centenary,  held  in  Berlin  in  May, 
1896,  Yirchow  stated,  as  an  ethnological  fact,  that  "  all 
peoples  that  had  not  been  reached  by  vaccination  or  that 
had  not  accepted  it  had  disappeared  from  the  face  of  the 
earth,  destroyed  by  smallpox."  Will  the  orator  of  1947 
be  able  to  point  to  a  triumph  of  American  medicine  equal 
to  the  application  of  anesthesia  a  hundred  years  before 
or  to  the  beginning  of  an  era  in  preventive  medicine,  like 
that  inaugurated  by  the  immortal  Jenner!  Looking  into 
the  future,  it  is  possible  that  in  fifty  years  smallpox  will 
have  disappeared  from  the  face  of  the  earth,  like  the  peo- 
ples it  has  destroyed.     But  who  can  say,  in  the  light  of 

*  Address  on  Medicine  delivered  at  the  semicentennial  anniversary  of  the 
American  Medical  Association,  in  Philadelphia,  June  2,  1897. 

258 


ANNIVERSARY   ADDRESS  259 

what  has  been  accompHshed  within  our  own  recollection, 
what  may  not  be  done  within  the  next  half-century!  In 
the  single  line  of  preventive  medicine,  is  it  not  possible 
that  we  may  be  able  to  secure  immunity  from  tuberculosis, 
typhus  and  typhoid  fevers,  scarlatina,  diphtheria  and  other 
infectious  maladies,  and  that  these  diseases  may  disap- 
pear! As  it  is  now,  even  with  a  not  inconsiderable  popu- 
lar prejudice  against  vaccination,  many  successive  years 
have  passed  in  the  city  of  New  York  without  one  case 
of  smallpox;  and  medical  knowledge  is  becoming  daily 
more  progressive  and  more  generally  accepted  by  the  laity. 

It  is  not  too  much  to  say  that  the  convention  of  May, 
1846,  marked  an  era  in  the  history  of  medical  organization 
in  the  United  States.  It  had  become  necessary  that  the 
medical  profession  should  be  unified  and  separated  from 
those  practising  under  sectarian  designations,  particularly 
as  at  least  one  sect  was  beginning  to  secure  the  confidence 
of  men  otherwise  intelligent,  and  assumed  to  practise  medi- 
cine on  a  scientific  basis.  Nearly  coincident  with  the  or- 
ganization of  this  Association  was  the  discovery  to  which 
I  have  already  alluded,  that  marked  a  grand  epoch  in 
the  history  of  American  medicine.  On  October  17,  1846, 
practically  the  first  surgical  operation  w'as  performed  un- 
der the  influence  of  an  anesthetic  administered  by  in- 
halation. Its  semicentennial  has  recently  been  impres- 
sively celebrated  at  the  IMassachusetts  General  Hospital, 
in  Boston.  There  are  few  who  remember  the  horrors  of 
severe  surgical  operations  and  the  agonies  of  dif^cult 
■childbirth  before  anaesthesia,  as  there  are  few  remaining 
who  participated  in  the  convention  which  organized  what 
is  now  the  American  Medical  Association;  but  all  can  real- 
ize what  surgery  would  be  W'ithout  artificial  insensibility 
to  pain,  and  w^hat  the  medical  profession  would  be  without 
a  National  Association. 

The  status  of  medicine  forty  years  ago  is  quite  within 
my  recollection.  Medicine  is  not,  never  was  and  never 
will  be  an  exact  science;  but  it  always  has  been  progres- 
sive and  never  more  so  than  at  the  present  time.  Fifty 
years  ago  perhaps  medicine  merited  the  reproach  of  being 
the  least  exact  of  all  sciences;  but  its  progress  within  the 
last  fifteen  years  has  been  so  prodigious  that  it  is  now  in 
advance  of  them  all.     The  Abbe  illuminating  apparatus 


26o  ANNIVERSARY   ADDRESS 

made  the  study  of  bacteria  possible;  and  this,  with  the 
wonderful  apochromatic  lenses,  as  it  now  appears  to  us, 
have  rendered  nearly  perfect  our  technical  means  of  his- 
tological and  bacteriological  research.  We  no  longer  dif- 
ferentiate and  separate  structures  by  the  coarse  methods 
of  actual  dissection  alone;  but  with  the  delicate  and  pre- 
cise instruments  used  in  cutting  thin  sections  and  by  stain- 
ing we  have  come  to  an  exact  knowledge  of  physiological 
and  pathological  histology,  which,  fifty  years  ago,  seemed 
unattainable.  Without  staining  fluids,  the  physiological 
and  pathological  histology  of  the  present  day  would  be 
impossible.  Fifty  years  ago  skill  in  the  diagnosis  of  cer- 
tain diseases  was  acquired  only  by  long  practice  and  large 
experience.  With  our  present  methods,  properly  em- 
ployed, it  is  impossible  to  make  an  error  in  the  diagnosis 
of  many  of  the  diseases  which  formerly  presented  difficul- 
ties, such  as  typhoid  fever,  tuberculosis,  diphtheria,  chol- 
era and  most  of  the  neoplasms.  To  say  that  pathology 
has  been  revolutionized  within  the  last  ten  or  fifteen  years 
is  not  enough — a  new  pathology  has  been  created,  and 
with  it  have  come  an  intelligent  hygiene,  prevention  and 
therapeutics,  based  upon  exact  scientific  knowledge. 

Eleven  years  ago  the  great  physician  whose  name  I 
bear  and  who  still  lives  in  the  memory  of  this  Association 
wrote  an  address  which  was  to  have  been  delivered  before 
the  British  Medical  Association,  entitled  Medicine  of  the 
Future.  This  classic  legacy  to  the  profession  he  so  loved 
and  adorned  embodied  recollections  of  a  half-century  of 
medical  observation,  with  a  prophetic  view  of  the  possibil- 
ities of  medicine  within  the  succeeding  half-century.  It 
was  difificult  for  this  wise  physician  to  restrain  his  predic- 
tions within  the  bounds  of  reasonable  enthusiasm.  The 
epoch-making  discovery  of  the  bacillus  tuberculosis,  an- 
nounced by  Koch  in  1882  and  graphically  described  and 
illustrated  by  Dr.  Belfield  before  this  Association,  at  the 
meeting  of  1883,  made  a  most  profound  impression  upon 
his  mind  and  imagination,  which  found  expression  in  an 
elaborate  paper  on  the  subject  read  in  January,  1884.  His 
predictions  of  possibilities  in  medicine  before  1936  are  now 
more  than  verified.  It  was  predicted  that  "  before  the 
lapse  of  another  half-century  there  will  be  another  era  in 
organic  chemistry,  and  that  light  will  penetrate  dark  re- 


ANNIVERSARY    ADDRESS  261 

cesses  which  histology  can  not  reach."  If  "  Hght  "  be  taken 
in  its  Hteral  sense,  is  not  this  more  than  realized  by  Ront- 
gen's  marvelous  discovery,  in  which  a  hitherto  unknown 
light  is  made  to  penetrate  opaque  matter  and  disclose  the 
invisil)le!  In  1886.  he  wrote:  "  Moreover,  there  are  pres- 
ent intimations  of  important  discoveries  respecting  inocu- 
lation W'ith  attenuated  viruses  and  contagia  in  order  to 
forestall  the  development  of  infectious  diseases.  Here 
open  up  to  the  imagination  the  future  triumphs  of  pre- 
ventive medicine  in  respect  to  all  classes  of  disease."  Now, 
little  more  than  ten  years  later,  serum-therapy  has  taken 
a  permanent  place  in  practice,  and  we  stand  on  the 
threshold  of  a  full  knowledge  of  immunity,  natural  and  ac- 
quired. 

As  no  human  imagination  fifty  years  ago  could  have 
pictured  the  condition  of  the  medicine  of  to-day,  so  it  to- 
day seems  impossible  to  imagine  its  progress  in  another 
half-century.  Never,  since  medicine  became  a  science,  has 
medical  history  been  made  so  fast  as  now-.  Between  the 
time  of  writing  and  of  delivering  this  address,  scientific 
labor  may  give  birth  to  a  discovery  destined  to  revolution- 
ize some  department  of  medicine,  as  Pasteur,  Koch  and 
their  follow^ers  have  revolutionized  therapeutics,  and  as 
Lister  has  created  a  new  surgery. 

The  reasonable  limits  of  an  anniversary  address  do 
not  permit  even  an  enumeration  of  the  greatest  of  the 
advances  in  the  science  of  medicine  since  the  organization 
of  this  Association,  much  less  their  discussion.  Your  ora- 
tor on  surgery  will  find  it  impossible  adequately  to  de- 
scribe the  progress  of  the  last  half-century  in  a  single 
address;  your  orator  on  state  medicine  can  hardly  com- 
pass the  wonderful  advances  made  even  in  the  single  line 
of  prevention  of  disease;  and  I  certainly  can  not  hope  to 
be  more  successful. 

It  is  a  matter  of  congratulation  that  the  name  of  this 
body  was  early  changed  from  National  to  "  American 
Medical  Association."  We  have  good  reason  to  be  proud 
of  American  medicine,  and  our  great  representative  asso- 
ciation may  properly  claim  a  distinctive  title.  When  one 
is  able  to  call  up  at  random  the  discoveries  in  gastric  di- 
gestion, anesthesia  in  surgery  and  obstetrics,  the  success- 
ful deligation  of  the  arteria  innominata,  the  operation  for 


262  ANNIVERSARY   ADDRESS 

vesico-vaginal  fistula,  o\-ariotomy  and  intestinal  anasto- 
mosis, to  say  nothing  of  minor  advances  in  medicine  and 
surgery,  can  we  not  claim  a  distinctive  place  for  American 
medicine!  It  is  in  the  United  States  that  advances  in  the 
science  of  medicine  find  the  most  ready  acceptance  and 
appreciation.  The  American  physician  is  the  most  intelli- 
gent and  judicious  therapeutist;  and  in  the  United  States 
are  the  best  and  safest  surgery  and  gynaecology. 

I  hope  to  see,  beginning  with  the  second  half-century 
of  the  American  Medical  Association,  a  more  complete 
unity  of  the  profession,  through  its  authority  and  influ- 
ence. In  the  matter  of  general  professional  welfare,  there 
seems  to  me  nothing  more  important  than  uniformity  in 
medical  legislation,  and.  so  far  as  possible,  in  educational 
requirements  preliminary  to  the  study  of  medicine  and 
for  license  to  practise  after  graduation.  Admitting  the 
proposition  that  the  profession  is  crowded,  it  is  evident 
that  this  condition  is  most  serious  in  the  large  cities;  but 
overcrowding  can  not  be  prevented  by  legislative  enact- 
ment, except  in  so  far  as  unqualified  men  are  excluded. 
Uniformity  of  legal  qualifications  to  practise  medicine  in 
the  different  States  can  best  be  secured  by  making  every 
State  society  actually,  as  well  as  nominally,  a  branch  of  the 
American  Medical  Association,  with  permanent  commit- 
tees from  each  State  organization  together  to  constitute  a 
central  legislative  body.  The  object  of  this  central  body 
should  be  to  secure  uniform  medical  laws  in  all  the  States, 
making  any  State  license  valid  for  all,  and  a  matriculation 
certificate  for  one  State  good  for  matriculation  in  all 
schools  represented  in  the  Association  of  American  Medi- 
cal Colleges.  A  certain  kind  of  medical  instruction  must 
be  concentrated  in  large  cities,  where  clinical  material  is 
abundant;  and  absolute  uniformity  of  curriculum  can  not 
exist  in  all  colleges;  but  certainly  the  legal  requirements 
for  practice',  as  determined  by  examination  by  State 
boards,  can  be  made  practically  identical  for  all  the  States. 
While  this  would  not  prevent  ambitious  young  men  from 
trying  their  fortunes  in  large  cities,  it  would  distribute 
well-qualified  physicians  more  equally  in  the  country  at 
large  and  tend  to  raise  the  standard  of  qualifications  and 
usefulness  of  the  average  country  doctor. 

It  is  the  prerogative  of  the  presiding  officer  of  this 


STERCORIN   AND    CHOLESTEREMIA  263 

association  to  make  recommendations,  and  this  is  not  the 
province  of  one  appointed  simply  to  give  an  anniversary- 
discourse.  At  the  jubilee  meeting  to  be  held  later  in  the 
session,  it  is  hoped  that  the  four  sundving  members  of  the 
convention  of  1846  will  be  present.  From  at  least  one 
of  these  you  may  expect  a  more  accurate  and  complete 
account  of  the  past  work  oi  the  association  and  a  more 
intelligent  view  of  its  probable  future  than  I  am  able  to 
give.  What  I  have  had  the  honor  to  present  I  well  know 
is  entirely  inadequate  to  the  occasion,  and  it  has  been 
given  merely  as  an  introduction  to  addresses  by  others, 
W'hich  will  be  much  more  suitable  and  interesting.  The 
remainder  of  the  time  that  has  been  placed  at  my  disposal 
I  shall  venture  to  occupy  with  a  subject  which  I  hope 
may  not  prove  entirely  unworthy  of  your  attention. 

STERCORIN  AND  CHOLESTEREMIA 

^^'hile  the  presentation,  on  this  occasion,  of  researches 
made  and  published  thirty-five  years  ago  (viewing  the 
question  from  a  physiological  standpoint)  calls  for  an  ex- 
planation and  perhaps  an  apology,  none  is  required  if  their 
great  importance  in  relation  to  the  pathology  of  the  liver 
is  considered,  especially  as  cholesteremia  is  by  no  means 
accepted  as  a  distinct  pathological  condition.  Were  it 
not  that  stercorin  has  just  been  rediscovered  in  Germany 
by  two  eminent  physiological  chemists,  who  make  no  men- 
tion of  its  full  description  in  1862  and  have  even  called 
it  by  another  name.  I  probably  should  not  have  repeated 
and  extended  my  original  observations.  As  it  is.  how- 
ever, I  feel  that  I  may  properly,  as  an  American  investi- 
gator, make  my  reclamation  before  the  American  ]\Iedical 
Association.  Although  my  paper,  published  in  the  "  Amer- 
ican Journal  of  the  Medical  Sciences  "  in  October,  1862, 
received  an  "  honorable  mention  ''  and  substantial  recog- 
nition from  the  Institute  of  France  and  my  observations 
have  been  verified  and  extended  by  French  and  German  in- 
vestigators, many  writers  on  physiology  and  pathology, 
even  the  most  recent,  fail  to  recognize  such  a  substance 
as  stercorin  and  in  treating  of  cholesterin  speak  of  its 
function  as  obscure   or  unknown.*      In    "  An   American 

*  Foster,  "A  Text-Book  of  Physiolog),"  New  York  and  London,  1S95,  p.  356 


264  STERCORIN    AND    CHOLESTEREMIA 

Text-Book  of  Physiology,"  Philadelphia,  1896,  cholesterin 
is  described  as  a  constant  constituent  of  the  bile,  very  wide- 
ly distributed  in  the  body  and  eliminated  by  the  liver-cells 
from  the  blood.  "  That  it  is  an  excretion  is  indicated  by 
the  fact  that  it  is  eliminated  unchanged  in  the  feces." 
Stercorin  is  not  mentioned.  As  a  matter  of  fact,  choles- 
terin does  not  occur  in  the  human  feces  in  health,  and  its 
presence  in  this  situation  is  exceptional. 

In  Hoppe-Seyler's  "  Zeitschrift  fiir  i)hysiologische  Che- 
mie,"  Strassburg,  1896,  is  a  paper  by  Bondzynski  and 
Humnicki  entitled  "  The  Destination  of  Cholesterin  in  the 
Animal  Organism."  The  authors  profess  to  have  discov- 
ered a  new  constituent  of  the  human  feces,  which  they 
call  "  koprosterin."  This  substance  is  identical  with  ster- 
corin, fully  described  in  1862.  The  reading  of  this  article 
led  me  to  repeat  the  original  researches  of  1862,  carrying 
them  out  by  the  methods  then  employed,  at  the  same  time 
repeating  the  observations  of  Bondzynski  and  Humnicki 
with  the  methods  and  appliances  used  in  their  work.  It 
is  mainly  an  account  of  these  new  observations  that  I  now 
give.  The  chemical  manipulations  were  done  by  Dr.  H. 
A.  Haubold,  assistant  to  the  chair  of  physiology  in  the 
Bellevue  Hospital  Medical  College,  and  J.  A.  Mandel,  as- 
sistant in  the  department  of  chemistry  in  the  College  of 
the  City  of  New  York  and  to  the  chair  of  chemistry  in 
the  Bellevue  Hospital  Medical  College.  To  these  two 
skillful  assistants  I  am  indebted  for  most  painstaking  and 
accurate  work  extending  over  a  period  of  several  months. 

The  original  stercorin,  of  which  specimens  obtained  in 
1862  are  in  my  possession,  was  extracted  from  the  human 
feces  by  the  following  process:  The  dried  and  pulverized 
feces  were  extracted  with  ether.  The  ethereal  extract  was 
passed  through  animal  charcoal  and  afterward  evaporated. 
The  residue  was  then  extracted  with  boiling  alcohol.  The 
alcoholic  extract  was  treated  with  potassium  hydrate  solu- 
tion, at  a  temperature  near  the  boiling  point  of  water,  in 
order  to  remove  the  fats  by  saponification,  which  were 
washed  out  with  water  until  the  filtrate  was  neutral  and 
perfectly  clear.  The  filter  was  dried,  extracted  with  ether, 
and  the  ethereal  extract  evaporated  to  dryness  and  ex- 
tracted with  boiling  alcohol.  The  stercorin  was  obtained 
from  the  alcoholic  extract  by  repeated  crystallization. 


STERCORIN    AND    CHOLESTEREMIA  265 

This  process  was  exactly  repeated  in  our  recent  ob- 
servations, and  at  the  same  time  stercorin  was  extracted 
by  the  process  described  by  Bondzynski  and  Humnicki. 
Normal  human  feces  were  obtained  to  the  amount  of  about 
fifty  pounds.  After  drying,  the  feces  were  divided.  Two 
analyses  each  were  made  by  Haubold  and  Mandel,  each 
one  extracting  stercorin  in  one  portion  by  the  original 
method,  and  in  the  other  by  the  new  method.  All  the 
extracts  obtained  were  identical  in  their  composition,  re- 
actions and  the  form  of  crystals.  It  was  fortunate  that  I 
had  for  comparison  a  fairly  large  specimen  of  stercorin 
extracted  in  1862,  and  a  microscopic  slide  bearing  the  date 
of  June,  1862,  in  which  the  crystals  were  perfect.  The 
product  obtained  by  my  process  was  a  little  more  abundant 
and  crystalHzed  rather  more  readily  than  that  obtained 
by  the  later  method. 

In  the  process  employed  by  Bondzynski  and  Hum- 
nicki, the  dried  feces  were  extracted  with  ether,  using 
Soxhlet's  extraction-apparatus.  The  fats  were  saponified 
with  sodium  alcoholate.  No  animal  charcoal  was  used. 
The  substance  was  purified  by  repeated  crystallizations. 
These  variations  from  the  original  method  are  unimpor- 
tant, except  in  so  far  as  they  expedite  the  process  of  ex- 
traction. The  form  of  the  crystals  and  the  reactions  were 
identical  with  those  which  I  obtained  for  stercorin  in  1862. 
Analyses  of  the  products  obtained  by  us,  full  details  of 
which  are  given  in  a  paper  sent  to  Hoppe-Seyler's  "  Zeit- 
schrift,"  gave,  for  stercorin,  the  formula,  C27H4SO,  the 
formula  found  for  cholesterin  being  C27H46O.  The  change 
of  cholesterin  into  stercorin  is  effected  by  the  addition 
to  the  former  of  two  atoms  of  hydrogen.  A  close  com- 
parison of  the  results  of  our  ultimate  analyses  with  those 
obtained  by  Bondzynski  and  Humnicki  shows  conclusively 
that  *'  koprosterin  "  and  stercorin  are  identical,  and  that 
stercorin  is  not  an  impure  cholesterin,  as  is  held  by  some 
eminent  investigators,  such  as  Hoppe-Seyler,  K.  B.  Hoff- 
mann and  others.  Stercorin  crystallizes  in  long,  fine  nee- 
dles which  radiate  from  a  centre,  forming  tufts,  and  which 
can  not  be  confounded  with  the  characteristic  crystals  of 
cholesterin.  In  a  chloroform  solution,  stercorin  gives,  with 
an  equal  volume  of  concentrated  sulphuric  acid,  first  a 
yellow  color  and  then  a  gradual  change  to  orange,  red  and 
18 


266  STERCORIN    AND    CHOLESTEREMIA 

finally  dark  red.  Treated  in  the  same  way,  cholesterin 
promptly  gives  a  blood-red  reaction  without  these  inter- 
mediate tints. 

The  o])inion  expressed  by  Hoppe-Seyler,  Hoffmann, 
and  indeed  many  others,  that  stercorin  simply  is  impure 
cholesterin,  can  not  have  been  based  upon  a  practical 
knowledge  of  this  substance.  Stercorin  has  a  well-defined 
formula  (C27H4f^O)  which  has  been  calculated  and  veri- 
fied by  the  formation  of  esters.  Its  crystals  are  quite  dif- 
ferent from  crystals  of  cholesterin  and  are  invariable  in 
form,  arrangement  and  color.  It  was  extracted  by  meth- 
ods practically  the  same  as  those  used  in  the  extraction 
of  cholesterin.  In  view  of  these  facts,  to  assume  that  ster- 
corin is  an  impure  substance  one  must  deny  a  positive  sci- 
entific basis  to  organic  chemistry. 

In  the  recent,  as  well  as  in  the  original  observations 
it  was  clearly  shown  that  cholesterin  is  changed  into 
stercorin  in  passing  down  the  intestinal  canal.  I  found 
that  this  change  involves  processes  incidental  to  intes- 
tinal digestion.  Cholesterin  and  no  stercorin  was  found 
in  the  feces  of  fasting  animals  and  in  the  meconium. 
Bondzynski  and  Humnicki  found  an  increased  proportion 
of  "  koprosterin  "  in  human  feces  after  the  ingestion  of 
a  certain  quantity  of  cholesterin.  They  also  showed  that 
cholesterin  united  readily  with  bromine,  while  "  kopros- 
terin "  formed  no  such  combination;  and,  indeed,  by  the 
use  of  bromine,  these  two  substances  may  be  separated 
when  they  exist  together.  They  confirmed  the  empirical 
formula  for  their  product  by  the  formation  of  a  number 
of  esters. 

In  1862  I  wrote:  "What  the  discovery  of  the  func- 
tion of  urea  has  done  for  diseases  which  now  come  under 
the  head  of  uremia,  the  discovery  of  the  function  of  cho- 
lesterin may  do  for  the  obscure  diseases  which  may  here- 
after be  classed  under  the  head  of  cholesteremia." 

It  is  now  generally  admitted  that  the  bile,  in  addition 
to  its  function  connected  with  digestion,  contains  one  or 
more  excrementitious  matters.  Taking  into  consideration 
the  various  ingredients  of  the  bile,  there  seems  to  be  but 
one  that  can  logically  be  compared  to  urea.  Cholesterin 
is  found  in  many  of  the  tissues  and  organs  of  the  body 
and  exists  in  the  blood.     Likening  it  to  urea,  it  becomes 


STERCORIN   AND    CHOLESTEREMIA  267 

a  question  whether  it  is  formed  in  the  liver  and  discharged 
in  the  bile  or  is  merely  separated  from  the  blood  by  the 
liver  and  excreted.  As  it  is  constantly  found  in  notable 
quantity  in  the  nervous  tissue,  in  the  proportion  of  eight 
to  twelve  parts  in  a  thousand,  it  occurred  to  me  to  ex- 
amine the  blood  of  the  internal  jugular  and  compare  the 
proportion  of  cholesterin  with  that  found  in  arterial  blood. 
In  one  experiment  on  a  dog,  the  blood  being  taken  with- 
out using  an  anesthetic,  I  found  an  increase  in  the  jugular 
over  the  carotid  of  nearly  sixty  per  cent.  In  an  etherized 
animal  the  increase  was  only  about  three  and  a  half  per 
cent.  In  another  dog,  not  etherized,  the  increase  was 
about  twenty-three  per  cent.  There  was  also  an  increase 
of  four  to  six  per  cent,  in  the  blood  of  the  femoral  vein 
over  arterial  blood.  In  three  cases  of  hemiplegia,  the 
blood  from  the  arm  of  the  sound  side  contained  about  the 
normal  proportion  of  cholesterin,  while  blood  from  the 
affected  side  contained  no  cholesterin. 

In  an  experiment  on  a  dog  it  was  found  that  the  arterial 
blood  lost,  about  twenty-three  per  cent,  and  the  portal 
blood  about  four  and  a  half  per  cent,  in  passing  through 
the  liver,  comparing  these  two  kinds  of  blood  with  blood 
taken  from  the  hepatic  vein. 

These  experiments  led  to  an  examination  of  the  feces 
to  determine  the  quantity  of  cholesterin  discharged;  but 
in  a  number  of  careful  examinations  of  many  different 
specimens  of  feces  I  was  unable  to  find  cholesterin.  I 
found,  however,  what  appeared  to  be  a  non-saponifiable 
fatty  substance  in  considerable  quantity.  Examining  this 
substance  daily  with  the  microscope,  after  five  or  six  days 
I  saw  crystals  beginning  to  form,  which  finally  presented 
the  appearances  I  have  already  described  as  characteris- 
tic of  stercorin.  I  found  the  daily  discharge  of  stercorin 
to  be  0.7  gramme,  about  equal  to  the  estimated  quantity 
of  cholesterin  discharged  into  the  intestine  in  the  bile  in 
the  twenty-four  hours.  In  but  one  examination  of  feces 
of  the  dog  did  I  find  cholesterin,  and  this  was  in  a  fasting 
animal,  a  small  qviantity  of  cholesterin  being  found  with 
stercorin.  In  a  specimen  of  meconium,  I  found  a  hundred 
and  sixty  parts  in  a  thousand,  of  cholesterin  and  no  ster- 
corin. In  clay-colored  feces  from  a  patient  with  jaundice 
from    obstruction,    neither    cholesterin  nor  stercorin  was 


268  STERCORIN    AND    CHOLESTEREMIA 

found.  In  the  feces  of  the  same  patient,  which  were  nor- 
mal in  color  and  obtained  fifteen  days  after  the  first  exam- 
ination, stercorin  was  found  and  no  cholesterin.  These 
experimental  facts  seemed  to  show  that  the  stercorin  of 
the  feces  was  derived  from  the  cholesterin  of  the  bile, 
and  that  the  change  of  cholesterin  into  stercorin  was  in- 
cidental to  the  processes  of  intestinal  digestion.  In  no 
case  was  I  able  to  detect  in  the  feces  any  trace  of  the 
biliary  salts. 

Passing  from  these  observations  to  the  pathological  re- 
lations of  cholesterin,  after  examining  three  specimens  of 
normal  blood  and  finding  the  proportion  of  cholesterin 
to  be  0.445  to  0-75I  o^  ^  P^^^  i^  ^  thousand,  examinations 
were  made  of  the  blood  of  patients  with  simple  jaundice 
and  those  with  what  is  called  icterus  gravis  the  cases  ter- 
minating fatally  with  grave  nervous  symptoms.  In  a  case 
of  sim])le  jaundice  terminating  in  recovery  at  the  end  of 
about  four  weeks,  the  blood  contained  0.508  of  a  part  in 
a  thousand,  well  within  the  limits  for  normal  blood.  In 
a  case  of  jaundice  with  cirrhosis  terminating  fatally  with 
serious  nervous  disturbance,  the  blood  taken  six  days  be- 
fore death  contained  1.850  part  in  a  thousand,  of  choles- 
terin, an  immense  increase  over  the  normal  proportion. 
In  this  case,  on  post-mortem  examination,  the  liver  was 
found  contracted,  and  the  gall-l3lad(ler  was  shrunken  con- 
taining only  about  seven  cubic  centimetres  of  bile. 

The  question  of  cholesteremia  has  been  much  discussed 
since  1862,  in  great  part  with  scant  approval  or  with- 
out acceptance.  However,  Picot,*  in  1872,  reported  a 
fatal  case  of  "  grave  jaundice  "  in  which  he  determined 
a  great  increase  in  the  proportion  of  cholesterin  in  the 
blood,  1.804  part  in  a  thousand.  Many  attempts  have 
been  made,  also,  to  produce  toxic  effects  by  injecting  cho- 
lesterin into  the  blood,  but  most  of  them  have  been  un- 
successful on  account  of  mechanical  obstruction  of  the 
blood-vessels.  In  1873,  however,  Koloman  Miiller  f  suc- 
ceeded by  injecting  cholesterin  rubbed  with  glycerin  and 
mixed  with  soap  and  water.  In  five  experiments  on  dogs, 
injecting  in  each  0.045  gramme  of  cholesterin,  he  pro- 

*  "Journal  de  I'anatomie,"  Paris,  1872,  tome  viii,  p.  246  et  seq. 
f  Ueber  Cholesteramie,     "  Arcbiv  flir  experimentelle  Pathologic  und  Phar- 
makologie,"  Leipzig,  1873,  Bd.  i.,  S.  213  et  seq. 


STERCORIN    AND    CHOLESTEREMIA  269 

duced   a   "  complete   picture   of   the    symptoms   of  grave 
jaundice." 

In  repeating  the  original  researches  of  1862,  the  ob- 
servations, as  regards  analysis  of  feces,  etc.,  were  some- 
what extended.  With  modern  apparatus,  the  manipula- 
tions may  be  freed  from  many  disagreeable  features  which 
heretofore,  probably,  have  interfered  with  this  line  of  in- 
vestigation. In  extracting  stercorin,  various  volatile  fatty 
acids  and  other  substances  were  removed,  the  constitu- 
tion and  relations  of  which  are  unknown.  \Ye  studied,  in 
this  connection,  some  of  the  products  of  bacterial  action, 
obtaining,  by  the  action  of  fecal  bacteria  on  proteids,  ska- 
tol  and  indol.  both  substances  containing  nitrogen.  It  is 
well  known  that  phenol  and  cresol  also  exist  in  the  feces. 
These  nitrogenous  matters  are  putrefactive  products; 
nothing  is  known  of  their  physiological  or  pathological 
relations,  and  up  to  this  time  stercorin  is  the  only  excre- 
mentitious  matter  yet  found  in  the  feces,  the  origin  and  re- 
lations of  which  are  at  all  understood.  Our  knowledge, 
indeed,  of  the  physiological  chemistry  of  the  feces  is  only 
just  begun;  and  we  may  look  to  future  investigations  for 
much  that  will  be  most  important  as  well  as  interesting. 
The  same  may  be  said,  in  a  measure,  of  the  bile  and  of  the 
true  pathology  of  certain  functional  and  structural  diseases 
of  the  liver.  How  long  shall  we  continue  to  speak  of 
biliousness,  congestion  or  torpor  of  the  liver,  the  classic 
liver-complaint,  "  et  id  genus  omne,"  using  terms  which 
have  no  scientific  meaning!  Undoubtedly  there  are  gen- 
eral disturbances,  dependent  upon  some  disorder  in  the 
functions  of  the  liver,  which  occur  without  jaundice,  and 
this  fact  has  long  been  recognized.  In  a  case  of  cirrhosis 
with  considerable  constitutional  disturbance  but  no  jaun- 
dice, the  blood  was  found  to  contain  an  excess  of  choles- 
terin,  0.922  of  a  part  in  a  thousand.  In  what  is  termed 
acholia,  there  may  be  grave  nervous  symptoms  without 
jaundice,  and  the  pathology  of  such  cases  is  unknown.  The 
biliary  salts  are  not  found  in  the  blood,  and  the  symptoms 
can  not  be  accounted  for  by  disturbances  in  digestion.  It 
is  possible  that  light  will  be  thrown  on  their  pathology  if  it 
is  admitted  that  there  is  a  condition  called  cholesteremia. 
As  yet  this  is  but  speculation;  but  if  the  theory  of  choles- 
teremia is  accepted,  a  wide  field  of  inquiry  is  opened  in  this 


270  STERCORIN   AND   CHOLESTEREMIA 

direction,  and  ere  long  we  may  speak  of  "  biliousness  "  and 
"  liver  complaint  "  with  some  definite  ideas  of  their  pa- 
thology. 

It  must  be  remembered  that  the  liver  is  by  far  the 
largest  gland  in  the  body;  that  it  secretes  a  fluid  which  is 
known  to  have  a  double  function,  one  connected  with  di- 
gestion and  the  other  with  the  elimination  of  cholesterin; 
that  the  blood  from  the  digestive  tract  all  passes  through 
this  organ,  where  it  undergoes  certain  changes;  that  it 
probably  stores  up  the  products  of  amylolytic  digestion  in 
the  form  of  glycogen;  that  it  arrests  certain  poisons,  and 
that  it  is  the  chief  organ  concerned  in  the  production  of 
urea,  which  is  discharged  by  the  kidneys.  It  may  have 
other  uses  in  what  is  now  called  internal  secretion,  in  ad- 
dition to  that  of  destruction  of  blood-corpuscles  and  the 
change  of  hemoglobin  into  bilirubin.  With  all  these 
known  varied  uses  of  the  liver,  however,  the  pathology 
of  hepatic  diseases  is  most  obscure.  We  do  not  know, 
even,  the  cause  and  mechanism  of  the  formation  of  gall- 
stones, which  are  often  composed  almost  entirely  of  cho- 
lesterin. 

The  term  acholia,  as  used  in  pathology,  now  means 
very  little  and  conveys  no  distinct  idea  of  the  causes  of 
the  nervous  symptoms  which  attend  this  condition.  The 
term  cholemia  is  generally  regarded  as  almost  synonymous 
with  jaundice.  If  cholesteremia  is  recognized  as  a  distinct 
pathological  condition,  with  symptoms  due  either  to  the 
accumulation  of  cholesterin  in  the  blood,  acting  as  a  toxic 
substance,  or  to  imperfect  separation  of  cholesterin  from 
the  nervous  tissue,  a  positive  advance  will  be  made  in  our 
knowledge  of  the  pathology  of  many  obscure  liver  dis- 
orders. 

The  quantitative  estimation  of  cholesterin  in  the  blood 
is  not  difficult,  and  it  does  not  require  more  than  four  to 
six  or  eight  grammes  of  blood.  The  only  tedious  ma- 
nipulations are  the  drying,  saponification  and  weighing; 
and  these  are  readily  done  in  a  well-appointed  laboratory. 
Some  process  may  be  devised  which  will  expedite  this  ex- 
traction. If  examinations  of  the  blood  were  to  be  made 
in  cases  of  obscure  nervous  disturbance,  in  epilepsy  and 
other  disorders  of  this  nature,  it  is  possible  that  cholesterin 
may  be  found  to  play  an  important  part  in  their  pathology. 


Fig.   3. — Stcrcurin,   U.   and   II.,  1897. 


fiG.  4. — Stercorin,  Flint,  1862,  recrystallized      Fig.  5. — Stercorin,  Flint,  original  slide 
in  1S97.  of  1S62. 

Photographs  by  Prof.  E.  K.   Dunham,  M.  D.     All  magnified  twenty  diameters. 


STERCORIN    AND    CHOLESTEREMIA  271 

The  fact  that  bromine  readily  combines  with  cholesterin, 
taken  in  connection  with  the  wide  use  of  the  bromides  in 
diseases  of  the  nervous  system,  is  very  suggestive.  May 
not  the  bromides  promote  the  ehmination  of  cholesterin, 
a  substance  which  is  so  insoluble  and  which  forms  few  com- 
binations! These  points  seem  well  worthy  of  the  consid- 
eration of  pathologists  and  therapeutists.  Certainly  the 
physiological  and  pathological  relations  of  cholesterin  offer 
a  wide  and  perhaps  fruitful  field  for  further  observation. 

With  this  paper  I  present  photographs  of  cholesterin, 
stercorin  extracted  by  the  original  method,  and  stercorin 
extracted  by  the  method  of  Bondzynski  and  Humnicki, 
all  in  1897,  with  a  photograph  of  crystals  obtained  in  1897 
from  a  specimen  of  stercorin  extracted  in  1862. 

I  have  added,  for  comparison  with  the  recent  crystal- 
lization from  the  specimen  of  1862,  a  photograph  from  a 
slide  marked  June,  1862.  These  crystals,  which  are  from 
the  same  specimen  of  1862,  have  been  mounted  for  thirty- 
five  years  and  are  much  more  abundant  and  beautiful  than 
those  obtained  by  recrystallization  in  1897. 


XII 

UEBER  STERCORIN 

(Aus  dem  physiologischen  Laboratorium  des  Bellevue  Hospital  Medical 
Colle^je  der  Stadt  Nevv-Vork.      Der  Redaction  zugegangen  am  3.  Juni,  1897.) 

Published  in  Hoppe-Seyler's  "  Zeitschrift  fiir  piiysiologische  Chemie,"^ 
August  28,  1897. 

In  Folge  einer  Mittheilung  der  Herren  Bondzynski 
und  Humnicki  "  Ueber  das  Schicksal  des  Cholesterins  im 
thierischen  Org-anismus  "  in  Band  XXII,  Seite  396-41Q 
dieser  Zeitschrift,  sehe  ich  mich  veranlasst,  aufs  Neue  auf 
meine  Beobachtungen  iiber  Stercorin  aufmerksam  zu  ma- 
chen. 

Die  Herren  Bondzynski  und  Humnicki  Ijeschreiben 
unter  dem  Namen  K  o  p  r  o  s  t  e  r  i  n  einen  neuen  Be- 
standtheil  der  menschlichen  Faeces.  Diese  Substanz  ist 
identisch  mit  dem  von  mir  im  Jahre  1862  entdeckten  und 
beschriebenen  Stercorin.  Da  die  genannten  Autoren 
zur  Darstellung  des  Koprosterins  dieselben  Processe  ange- 
wandt  und  zu  denselben  Resultaten  gelangt  sind  wie  ich^ 
so  erscheint  es  mir  angebracht,  meine  friiheren  Arbeiten  im 
Vergleich  mit  den  Versuchen  von  Bondzynski  und  Hum- 
nicki zu  besprechen. 

Beim  Lesen  der  Arbeit  von  Bondzynski  und  Humnicki 
erscheint  es,  als  ob  dieselben  glauben.  eine  neue  Substanz 
im  Koprosterin  entdeckt  zu  haben.  Es  wird  des  Stercorins 
und  seines  Entdeckers  keine  Erwahnung  gethan,  obgleich 
das  zuerst  von  mir  beschriebene  Stercorin  in  der  deutschen, 
franzosischen  und  englischen  Literatur  seit  1862  in  mehr 
oder  weniger  vollstandigen  Berichten  iiber  dessen  Eigen- 
schaften  und  seine  Beziehungen  zum  Organismus  erwahnt 
wird. 

Meine  Originalmittheilung  wurde  im  Jahre  1862  im 
"  American  Journal  of  the  Medical  Sciences  "  in  Philadel- 
phia veroffentlicht  unter  dem  Titel  "  Experimental  Re- 
searches into  a  new  Excretory  Function  of  the  Liver.'^ 
272 


UEBER   STERCORIN  273 

Diese  Function  besteht  in  der  Abgabe  von  Cholesterin  aus 
dem  Blut  und  seiner  Ausscheidung  aus  dem  Korper  in  der 
Form  von  Stercorin.  Im  Jahre  1868  wurde  von  G.  Bailliere 
in  Paris  eine  Uebersetzung  ins  Franzosische  veroffentlicht, 
und  im  Jahre  1869  erhielt  das  Werk  bei  der  Bewerbung 
um  den  Preis,  der  Villemins  Arbeit  iiber  die  Contagiositat 
der  Tuberculosis  zuerkannt  wurde,  eine  "  ehrenvolle  Er- 
wahnung  "  und  eine  Belohnung  von  1500  Francs  vom  In- 
stitut  de  France.  Seit  der  Zeit  sind  ausfiihrliche  Berichte 
liber  Stercorin  erschienen  in  einem  meiner  Vortrage,  ver- 
offentlicht in  den  "  Transactions  of  the  International  Med- 
ical Congress,"  Philadelphia  1876,  in  meinem  Werke 
"  Physiology  of  Man  "  in  5  Banden  und  in  meinem  Hand- 
buch  "  Human  Physiology,"  von  welchem  allein  mehr  als 
20,000  Exemplare  verbreitet  worden  sind;  kurze  Erwah- 
nungen  findet  man  fast  in  alien  medicinischen  Lexika  und 
in  Werken  iiber  Pathologie,  Physiologie  und  medicinische 
Chemie.  Die  Anerkennung,  die  den  griindlichen  und  ex- 
acten  Untersuchungen  von  Herren  Bondzynski  und  Hum- 
nicki  gezollt  werden  muss,  kann  nicht  auch  auf  deren  Be- 
kanntschaft  mit  der  Literatur  des  Gegenstandes  ihrer  For- 
schungen  ausgedehnt  werden.  Ware  es  anders,  so  wiirde 
ich  nicht  gezwungen  sein,  das  Recht  eines  ersten  Beobach- 
ters  auszuiiben,  nach  welchem  ich  Prioritat  beanspruche 
und  fordere,  dass  der  Name  "  Koprosterin  "  durch  "  Ster- 
corin "  ersetzt  werde. 

Das  urspri^ingliche  Stercorin,  von  welchem  ich 
Praparate  in  meinem  Besitz  habe,  wurde  durch  folgenden 
Process  aus  menschlichem  Koth  gewonnen. 

Die  getrockneten  und  pulverisirten  Faeces  wurden  mit 
Aether  extrahirt.  Das  atherische  Extract  wurde  durch 
Thierkohle  entfarbt  und  dann  verdunstet.  Der  Ritckstand 
wurde  darauf  mit  kochendem  Alkohol  ausgezogen,  das 
alkoholische  Extract  mit  einer  Kalihydratlosung  bei  einer 
etwas  unter  dem  Siedepunkt  des  Wassers  liegenden  Tem- 
peratur  verseift,  zur  Entfernung  der  Seifen  mit  Wasser 
gewaschen,  bis  das  Filtrat  neutral  und  vollkommen  klar 
war.  Das  Filter  wurde  dann  getrocknet,  mit  Aether  aus- 
gezogen, das  atherische  Extract  zur  Trockne  verdampft 
und  mit  kochendem  Alkohol  extrahirt.  Das  Stercorin 
wurde  aus  dem  verdunsteten  alkoholischen  Extract  durch 
wiederholte  Krystallisation  aus  Alkohol  gewonnen. 


274  UEBER   STERCORIN 

Dieser  Process  wurcle'  audi  bei  clcn  ncucn  Versiichen 
wiederholt  und  das  erhaltene  Produkt  ergab  bei  der  Ele- 
mentar-Analyse  die  folgenden  Resultate: 

Nr.     I.  Substanz  0,2781  gr.;  €02:0,8521  gr.,  H2O:  0,3064  gr. 
Nr.  II.  „  0,2437    „        „       0,7461    „         „      0,2701    „ 

entsprechend 

Nr.   I  Nr.  2 

Kohlenstoff     83,56^  83,49^ 

Wasserstoff     12,245^  12,31^ 

wahrend  Bondzynski  und  liumnicki  das  Folgende  fiir  ihr 
"  Koprosterin  "  fanden: 

1.  Substanz  0,3242  gr.,  €02:0,9908  gr.,  H2O  :  0,3595  g^- 

2.  „  0,2954    „        „       0,9035    „         „       0,3255    „ 

3.  „  0,2684   "        "       0,8224    „         „       0,2968    „ 


entsprechend 

I. 

Kohlenstoff     83,24 
Wasserstoff     12,24 

83.41 
12,24 

83^56 
12,21 

Beim  Vergleichen  dieser  beiden  Reihen  von  Resultaten 
ist  es  ersichtlich,  dass  die  nach  meiner  Originalmethode 
isolirte  Substanz  mit  Koprosterin  identisch  ist. 

Stercorin  krystallisirt  in  langen,  feinen  Nadeln,  die  von 
einem  Centrum  ausstrahlen  und  Biischel  bilden,  und  diese 
Krystalle  konnen  gar  nicht  mit  Cholesterinkrystallen  ver- 
wechselt  vverden,  wie  von  einigen  Forschern,  wie  Hoppe- 
Seyler,  K.  B.  Hoffmann  u.  a.,  behauptet  worden  ist. 

Die  Reactionen  des  Stercorins  sind  mit  denen  des  "  Ko- 
prosterins  "  identisch,  in  Chloroformlosung  gibt  es  nam- 
lich  mit  einem  gleichen  Volumen  cone.  Schwefelsaure 
zuerst  eine  gelbe  Farbe,  welche  beim  Stehen  sich  langsam 
in  eine  orangerothe  und  dann  in  dunkelrothe  Farbe  um- 
wandelt. 

Liebermanns  Reaction  gibt  mit  einer  Chloroformlo- 
sung von  Stercorin  sofort  eine  blaue  Farbe,  die  bald  von 
einer  griinen  gefolgt  wird. 

In  dem  von  Bondzynski  und  Humnicki  angewandten 
Process  wurden  die  getrockneten  Faeces  vermittelst  Soxh- 
lets  Extractionsapparat  mit  Aether  extrahirt,  Die  Fette 
wurden  mit  Natriumalkoholat  verseift.  Thierkohle  wurde 
nicht  angewendet,  sondern  die  Substanz  wurde  durch  wie- 
derholte  Krystallisation  gereinigt.     Diese  Abweichungen 


UEBER   STERCORIN  275 

von  meiner  urspriinglichen  Methode  sind  unwesentlich,  sie 
beschleunigen  nur  den  Extractionsprocess.  Das  nach 
dieser  Methode  erhaltene  Produkt  ist  sowohl  beziiglich 
der  Krystallform  wie  auch  der  chemischen  Eigenschaften 
mit  Stercorin  identisch.  Die  Feststellung  dieser  That- 
sachen  ist  geniigend  und  es  ist  iiberfliissig,  der  ausserst 
sorgsamen  Arbeit  der  Herren  Bondzynski  und  Humnicki 
Weiteres  hinzuzufiigen. 

In  meinen  neuen,  ebenso  wie  in  den  friiheren  urspriing- 
lichen Beobachtungen,  habe  ich  klar  nachgewiesen,  dass 
Cholesterin  beim  Durchgang  durch  den  Darmkanal  in 
Stercorin  umgewandelt  wird.  Ich  fand,  dass  diese  Veran- 
derung  auf  den  Processen  der  Darmverdauung  beruht. 
Cholesterin  und  kein  Stercorin  wurde  in  dem  Koth  von 
fastenden  Thieren  und  im  Meconium  gefunden.  Bond- 
zynski und  Humnicki  fanden  nach  Einnahme  einer  be- 
stimmten  Alenge  Cholesterin  eine  vermehrte  Menge  Ko- 
prosterin  in  den  menschlichen  Faeces. 

Diese  Forscher  berechneten  die  Formel  Co-H4gO  fiir 
"  Koprosterin  "  und  Co-j^i^^O  als  Formel  fiir  Cholesterin. 
Hieraus  ergibt  sich,  dass  die  Veranderung  des  Choleste- 
rins  in  "  Koprosterin  "  auf  dem  Eintritt  von  zwei  Atomen 
Wasserstofif  beruht.  Sie  zeigten  auch,  dass  das  "  Kopro- 
sterin "  keine  Verbindungen  mit  Brom  bildet,  wie  dies 
beim  Cholesterin  der  Fall  ist.  Durch  Brom  konnen  auch 
diese  beiden  Substanzen  getrennt  werden,  wenn  sie  zusam- 
men  vorkommen. 

Die  Beobachtungen  von  Bondzynski  und  Humnicki 
w'aren  rein  chemischer  Natur.  In  meiner  Originalarbeit 
untersuchte  ich  zunachst  die  physiologischen  Eigenschaf- 
ten und  Beziehungen  der  Galle  in  ihrer  Bedeutung  sowohl 
fiir  die  Verdauung  und  Resorption  als  auch  fiir  die  Excre- 
tion. Ich  studirte  dann  das  Cholesterin,  wie  es  in  gewissen 
Organen,  Geweben  und  Fliissigkeiten  des  Korpers  gefun- 
den wird.  Ich  zeigte,  dass  die  Menge  des  Cholesterins  im 
Blute  vermehrt  wird  bei  dem  Durchgang  des  letzteren 
durch  das  Gehirn  und  verhaltnissmassig  verringert  wird 
beim  Durchgang  durch  die  Leber,  und  wies  nach,  dass 
Cholesterin,  wenn  es  ein  Ausscheidungsprodukt  ist,  w^ahr- 
scheinlich  zum  grossten  Theil  das  Resultat  von  Umsetzun- 
gen  im  Nervengewebe  ist. 

Dann  zeisite  ich  die  Verwandlunsf  des  Cholesterins  im 


276  UEBER    STERCORIN 

Diinndarm  unci  entdeckte  Stercorin  in  den  Faeces  in  einer 
Quantitiit,  die  der  Menge  des  in  der  Galle  ausgeschiedenen 
Cholesterins  fast  gleich  kam. 

Eine  Entschuldigung  dieses  Prioritatsansprtichs  auf  die 
Entdeckung  des  Stercorins  als  eines  Bestandtheils  der 
Faeces  tind  dieses  Protestes  gegen  den  Namen  "  Kopro- 
sterin  "  mag  aiis  der  hohen  Wichtigkeit  der  Beziehung 
dieser  Siibstanz  ziim  Cholesterin  und  aus  der  grossen  Be- 
deiitung  des  von  mir  als  Cholesteraemie  bezeichneten 
Krankheitszustandes  hergeleitet  werden. 

Ich  bin  weit  davon  entfernt,  irgend  einen  Vorwiirf  ge- 
gen die  Herren  Bondzynski  und  Humnicki  zu  beabsichti- 
gen,  ich  bin  ihnen  sogar  zu  Dank  verpflichtet,  da  ihre  von 
den  meinen  unabhangigen  Beobachtungen  wahrscheinlich 
veranlassen  werden,  dass  die  Existenz  des  Stercorins  und 
der  Cholesteraemietheorie  die  allgemeine  Anerkennung 
findet,  auf  welche  ich,  mit  wenig  oder  gar  keiner  Ermuthi- 
gung,  35  Jahre  gewartet  habe. 

Zu  gleicher  Zeit  nehme  ich  Veranlassung,  meinen  As- 
sistenten,  den  Herren  H.  A.  Haubold  und  J.  A.  Mandel, 
meinen  Dank  auszusprechen  fiir  ihre  gewissenhaften  und 
anerkennenswerthen  Arbeiten  bei  der  Wiederholung  der 
urspriinglichen  Darstellung  des  Stercorins. 


XIII 

ON  THE  ORGANIC  NITROGENOUS  PRINCIPLES 
OF  THE  BODY  WITH  A  NEW  METHOD  FOR 
THEIR   ESTIMATION   IN  THE   BLOOD 

PART   I 

Published  in  the  "  American  Journal  of  the  Medical  Sciences  " 
for  October,  1863. 

Composition  and  Properties  of  the  Organic 
Nitrogenous  Principles  of  the  Body. — The  physi- 
ological investigator  of  the  present  day  is  greatly  depend- 
ent upon  chemistry  for  methods  of  investigating  the  func- 
tions of  the  body;  so  much  so,  indeed,  that  these  depart- 
ments can  not  be  separated  from  each  other;  and  it  is  to 
physiological  chemistry  he  must  look  for  the  solution  of 
questions  of  the  highest  importance  which  yet  remain 
unanswered.  Of  the  various  questions  which  thus  re- 
main to  be  answered  by  the  chemist,  that  of  the  quantity, 
composition,  condition  of  existence  and  changes  of  the 
organic  nitrogenous  principles  is  the  most  important;  for 
these  apparently  are  the  constituents  of  the  body  endowed 
with  vital  properties;  they  regulate  the  changes  which  take 
place  in  the  other  principles,  and  the  various  modifications 
which  they  undergo  in  the  body  constitute  the  mysterious 
''  life,"  the  comprehension  of  which  has  not  yet  been  grant- 
ed to  the  student  of  Nature.  Though  chemistr}^  has  en- 
abled the  physiologist  to  make  but  little  if  any  progress 
toward  the  solution  of  the  great  question  of  vitality,  it  has 
helped  him  to  comprehend  certain  of  the  phenomena  of 
living  bodies;  and  by  long  searching  he  has  found  out  some 
of  the  laws  which  regulate  their  phenomena.  The  results 
of  the  physiological  labors  of  centuries  have  only  confirmed 
an  axiom  which  must  be  recognized  by  every  one  who 
hopes  to  make  any  advance  in  this  science. 

The  laws  which  regulate  animated  Nature  are  irrevo- 

277 


278  ORGANIC    NITROGENOUS    PRINCIPLES 

Ccibly  fixed;  as  distinct  from  those  which  g-overn  inanimate 
objects  as  life  is  from  death.  They  must  be  sought  for  by 
a  patient  study  of  the  phenomena  of  Hfe,  until  the  chain 
of  evidence  is  complete.  The  mind  must  seek  to  compre- 
hend, not  to  create. 

Much  ineffectual  labor  has  resulted  from  a  lack  of  com- 
prehension of  this  idea.  While  physiology  was  com- 
paratively new  as  a  science,  many  endeavored  to  establish 
laws  for  the  regulation  of  the  economy  instead  of  add- 
ing to  actual  knowledge  of  phenomena;  and  others, 
ignorant  of  the  fact  that  what  is  true  of  inanimate  matter 
can  not  be  applied  to  the  Hving  body,  endeavored  to  explain 
everything  by  physical  or  chemical  laws.  To  this  latter 
may  be  attributed  the  want  of  application  of  chemistry  to 
physiology  until  within  the  last  few  years;  though,  in  all 
ages,  when  learning  has  been  cultivated,  chemistry  has 
been  a  favorite  study.  Those  who  took  such  pride  in  the 
discovery  of  elements  and  the  establishment  of  physical 
laws  could  not  bring  themselves  to  admit,  and  can  not  at 
the  present  day  admit  that  the  body  is  anything  but  a  col- 
lection of  elements  regulated  by  the  laws  with  which  they 
are  familiar;  while  those  who  saw  these  laws  so  often 
violated  in  living  bodies  were  disposed  to  reject  entirely 
chemical  and  physical  explanations  of  physiological  phe- 
nomena. To  make  use  of  chemistry,  from  which  physi- 
ology had  so  much  to  expect,  it  was  necessary  to  cre- 
ate a  new  method  of  study  which  would  have  reference  to 
organic  substances  and  to  substances  not  necessarily  chem- 
ical elements  but  formed  from  these  elements,  which  are 
now  called  proximate  principles.  It  will  be  seen  at  once 
how  important  are  these  principles  with  reference  to  their 
condition  and  behavior  in  the  living^  body,  and  how  neces- 
sary it  is  to  study  them  from  this  point  of  view  and  not 
sim.ply  as  inorganic  or  inanimate  compounds. 

There  is  thus  a  manifest  difference  between  proximate 
principles  and  chemical  elements.  The  former  have  certain 
properties  in  the  living  body  which  are  different  from  any 
known  in  the  inorganic  world.  They  may  have  properties 
peculiar  to  animal  substances,  like  albumin  or  myosin, 
which  are  endowed  in  living  bodies  with  the  vital  properties 
of  continual  destruction  and  reparation;  or  the  substance 
may  be  inorganic,  as  water  or  chloride  of  sodium,  but  actu- 


ORGANIC   NITROGENOUS   PRINCIPLES         279 

ally  entering  into  the  composition  of  organized  tissues  and 
participating  in  the  peculiar  changes  which  they  undergo. 
The  latter  are  indivisible  substances,  possessing  no  power 
of  self-regeneration,  forming  definite  compounds  by  union 
with  other  elements  of  the  same  class,  by  which  union  the 
properties  of  the  component  parts  are  radically  changed. 
Chemical  elements  can  be  studied,  and  have  been  studied 
for  years,  without  reference  to  organized  or  living  struc- 
tures; though  these  are  formed  necessarily  of  such  ele- 
ments, and  as  such  have  been  found  to  possess  certain 
definite  properties.  When  the  chemist,  in  investigating 
organic  bodies,  studies  only  the  ultimate  elements  of  which 
they  are  composed,  he  learns  nothing  more  of  the  proper- 
ties of  these  elements,  for  they  are  identical  with  those  he 
extracts  from  inorganic  substances.  He  gives  simply  the 
results  of  decomposition  of  the  body;  but  w^iat  the  physi- 
ologist wishes  to  know  is  the  function  of  the  systems 
and  organs  and  the  elements  which  compose  the  tissues  of 
the  body.  The  viltimate  composition  of  organic  bodies  is 
manifestly  of  little  importance  compared  with  a  knowledge 
of  their  physiological  properties;  unless,  indeed,  this  should 
explain  their  function,  a  hope  of  the  chemist  which  is  rarely 
realized.  Thus  the  body  can  not  advantageously  be  studied 
from  a  purely  chemical  point  of  view;  and  the  changes 
which  take  place,  even  in  its  inorganic  constituents,  can 
not  be  explained  by  formulas  which  indicate  simply  the 
addition  or  subtraction  of  certain  elements.  Within  a  few 
years  a  great  advance  has  been  made  in  physiological  chem- 
istry by  a  modification  of  the  method  of  study  of  organic 
matters.  The  most  rational  investigators  of  the  present 
day  treat  them  as  compound  substances,  which  can  not  be 
decomposed  without  destroying  their  peculiar  properties. 
But  a  still  further  advance  is  necessar}':  they  must  be  con- 
sidered, not  merely  as  proximate  principles,  which  can  be 
separated  from  the  body  by  means  which  do  not  interfere 
with  their  chemical  composition,  but  as  principles  capable 
of  performing  their  functions  only  when  united  together, 
as  they  certainly  are  in  Nature.  For  example,  what  has 
been  considered  as  albumin,  that  is,  dried  albumin,  is  in- 
capable of  performing  its  function  if  it  is  not  united  w'ith 
water,  chloride  of  sodium  and  other  inorganic  substances 
which  are  always  found  in  connection  with  it;  and  though 


28o  ORGANIC   NITROGENOUS    PRINCIPLES 

it  is  important  to  know  its  ultimate  composition  and  its 
behavior  on  the  application  of  heat,  in  the  presence  of  acids, 
etc.,  etc.,  these  phenomena  are  artificial  and  useful  only 
as  tests.  The  true  line  of  incjuiry  lies  in  a  study  of  its  be- 
havior in  the  body  and  the  investigation  of  natural,  rather 
than  artificial  phenomena.  Instead  of  attempting  to  isolate 
it  completely,  it  should  rather  be  studied  in  its  union  with 
the  other  principles  by  which  it  is  enabled  to  perform  its 
functions;  and  when  it  is  separated  from  the  animal  fluids 
in  order  to  ascertain  its  proportional  quantity,  it  should  be 
separated  with  those  other  substances  which  are  united 
with  it  in  the  living  body  and  without  which  it  can  per- 
form no  vital  functions.  It  will  be  seen  that  some  of  these 
substances,  as  water,  actually  enter  into  the  composition 
of  the  organic  principles  and  can  not  be  separated  without 
alteration  and  decomposition. 

These  preliminary  remarks  explain  why  I  consider  it 
of  the  greatest  importance  to  study,  first  of  all,  the  condi- 
tion under  which  organic  substances  exist  in  the  body,  espe- 
cially as  this  question  is  almost  ignored  by  physiologists. 
To  correspond  with  the  ideas  I  shall  present  upon  this 
question,  a  new  method  of  estimating  the  quantities  of 
these  substances  is  necessary,  as  the  ordinary  analyses  are 
the  work  of  chemists  who  have  not  appreciated  their  con- 
dition of  existence.  In  discussing  this  question  I  shall  re- 
view to  some  extent  the  opinions  and  analyses  of  chem- 
ists, which  are  accepted  at  the  present  time. 

Ultimate  Composition  of  Organic  Nitrogenous 
Substances. — According  to  the  present  views,  every 
tissue  of  the  body  and  all  the  fluids,  with  the  exception 
of  the  excrementitious  fluids,  contain  a  characteristic  ele- 
ment, which  is  found  in  no  other  situation  and  which 
gives  certain  properties  connected  with  nutrition,  which 
may  be  called  vital.  These  tissues  and  organized  fluids 
contain  usually  but  one  characteristic  organic  principle. 
With  the  exceptions  of  the  blood  and  milk,  there  is  but 
one  such  element  to  each  tissue  or  fluid.  The  blood,  how- 
ever, which  furnishes  the  material  for  the  formation  of 
all  these  substances,  contains  several  organic  principles; 
viz.,  fibrin,  albumin,  and  globulin;  and  the  milk  contains, 
in  addition  to  casein,  a  trace  of  albumin.  Although  it  is 
probable  that  all  the  tissues  and  organized  fluids  (excre- 


ORGANIC    NITROGENOUS    PRINCIPLES  281 

mentitious  fluids  excepted)  contain  principles  of  this  kind, 
whicli  are  characteristic  and  present  shades  of  difference  for 
each  one,  some  have  not  yet  been  separated  sufficiently 
for  purposes  of  study;  and  according  to  Robin  and  Verdeil, 
only  seventeen  can  be  regarded  as  well  established.* 

LIST   OF   ORGANIC   NITROGENOUS   SUBSTANCES 
Name.  Where  found. 

Fibrin Blood,  chyle,  lymph. 

Albumin Blood,  chyle,  lymph,  serum,  milk. 

Albuminose Chyme,  blood. 

Casein Milk. 

Mucosine Mucus. 

Pancreatine Pancreatic  juice. 

Globuline Blood-globules. 

Musculine Muscles. 

Osteine Bone. 

Cartilageine Cartilage. 

Elasticine Elastic  tissue. 

Keratine Nails,  hair,  epidermis. 

Crystalline Crystalline  lens. 

f  Hematine Coloring  matter  of  the  blood. 

,  J  Biliverdine "  "  "       bile. 

'  ]  Urosacine "  "  "       urine. 

1^  Melanine "  "  "       pigment. 

Of  the  seventeen  principles  above  enumerated,  only 
three  have  been  studied  with  any  degree  of  accuracy;  name- 
ly, fibrin,  albumin  and  casein.  The  proportion  of  these 
principles  in  the  fluids  in  which  they  have  been  found  has 
been  carefully  estimated;  and  in  addition  much  pains  has 
been  bestowed  upon  their  ultimate  analysis.  Albumin  has 
given  the  name  to  nearly  all  these  substances,  from  simi- 
larity, as  far  as  known,  of  composition,  and  the  others,  called 
albuminoids,  have  been  simply  indicated  in  the  situations 
above  enumerated,  no  attempt  having  been  made,  with 
one  or  two  unimportant  exceptions,  to  estimate  their  quan- 
tity or  to  ascertain  their  ultimate  composition.  In  fine,  the 
blood  and  the  milk  are  about  the  only  fluids  of  the  body 
which  have  been  subjected  to  critical  analysis  for  organic 
substances,  and  hardly  anything  has  been  done  with  the 
solids.  I  do  not  propose  in  this  article  to  take  up  the 
chemistry  of  the  milk;  and  throwing  out  this  fluid,  I  am 
reduced  in  my  examination  of  analyses  to  the  organic  prin- 

*  "  Traite  de  chimie  anatomique,"  Paris,  1853. 

+  These  are  simply  coloring  matters  and  are  put  by  Robin  and  Verdeil  in 
this  class  as  they  contain  nitrogen. 

19 


282  ORGANIC   NITROGENOUS   PRINCIPLES 

ciples  of  the  blood,  which  have  justly  claimed  the  most 
careful  investigation  at  the  hands  of  physiological  chemists. 
In  the  latter  part  of  the  last  century  Bertholet  demon- 
strated the  existence  of  nitrogen  in  organic  bodies.  Before 
his  time  chemists  had  little  idea  of  their  composition.  It 
was  known  that  they  were  very  unstable,  and  the  discovery 
of  the  al)Ove-named  ingredient  offered  a  supposed  explana- 
tion of  this  fact;  viz..  that  its  presence  engendered  a  num- 
ber of  "  attractions  "  which  did  not  operate  in  bodies  of  a 
less  complicated  composition.  This  discovery  was  a  great 
advance  in  the  chemical  knowledge  of  organic  substances 
of  this  class;  and  the  researches  of  investigators  since  that 
time  have  so  far  established  it,  that  they  are  known  gener- 
ally under  the  name  of  nitrogenous,  or  azotized  principles. 
The  organic  matters  were  afterward  closely  studied  by  Du- 
mas, especially  those  existing  in  the  blood;  and,  indeed,  the 
mode  of  analysis  of  this  fluid  for  its  organic  constituents, 
employed  by  Dumas  forty  years  ago,  is  the  one  adopted, 
with  but  slight  modifications,  by  chemists  of  the  present 
day.  He  ascertained,  in  the  first  place,  the  quantity  of 
water  which  could  be  driven  ofT  from  the  blood,  and  attrib- 
uted it  all  to  the  serum,  considering  the  fibrin  and  albu- 
min as  held  in  solution  by  this  water  and  the  globules  as 
possessing  no  fiuid  of  their  own.  By  appropriate  means, 
which  will  be  considered  hereafter,  he  separated  the  fibrin, 
albumin  and  glol)ules,  evaporated  them  to  dryness  and  esti- 
mated them  in  this  condition.  The  ultimate  composition 
of  these  principles  was  not  then  definitely  ascertained;  and 
no  theory  of  the  mode  of  union, of  their  elements  or  their 
formation  was  proposed.  A  few  years  later  (1837),  in  con- 
nection with  Liebig,  Dumas  proposed  a  division  of  chem- 
ical science  into  inorganic,  or  mineral,  and  organic.  Ac- 
cording to  the  theory  proposed,  all  inorganic  bodies  were 
composed  of  two  elements  directly  combined,  forming 
what  they  called  binary  compounds,  which  again  united 
with  other  compounds  formed  in  the  same  way.  Thus, 
potassium  and  oxygen  united  to  form  potash  (KO),  which, 
in  its  turn,  can  unite  with  another  binary  compound,  as 
nitric  acid  (NO5),  to  form  nitrate  of  potash  (KO.NO5); 
the  elements  first  uniting  together  to  form  pairs,  which  in 
their  turn  unite  with  each  other.  In  inorganic  chemistry 
the  union  of  elements  proceeds  in  this  simple  manner  to 


ORGANIC    NITROGENOUS    PRINCIPLES  283 

form  the  most  complex  substances;  an  element  can  unite 
only  with  an  element,  a  binary  compound,  with  a  binary 
compound,  and  so  on.  Organic,  particularly  vegetable  sub- 
stances, on  the  contrary,  were  theoretically  reduced  to  the 
compounds  of  a  radicle  which,  though  itself  a  compound, 
behaved  toward  elementary  substances  in  the  same  way 
as  a  simple  inorganic  element.  In  other  words,  the  beha- 
vior of  these  so-called  organic  radicles  in  their  union  wdth 
elementary  substances  would  lead  one  to  suppose  them  to 
be  elements  themselves;  it  is  only  chemical  analysis  which 
shows  them  to  be  compound.  For  example,  cyanogen  will 
unite  with  hydrogen  to  form  hydrocyanic  acid  (HCy),  as 
chlorine  will  unite  w-ith  hydrogen  forming  hydrochloric  acid 
(HCl).  The  latter  is  an  inorganic  or  mineral  acid,  and  the 
chlorine,  which  is  the  radicle,  is  of  necessity  an  elementary 
substance;  but  cyanogen,  the  radicle  of  the  organic  acid, 
though  it  unites  with  the  element  hydrogen  in  the  same 
way  as  the  chlorine,  behaving  like  an  elementary  substance, 
is  found  by  chemical  analysis  to  be  a  compound  of  carbon 
and  nitrogen  (CN).  It  is  in  reality  a  radicle,  but  com- 
pound; and  a  compound  radicle  is  a  thing  unknown  in 
inorganic  chemistry.  The  example  just  given  shows  a 
marked  difference  in  the  behavior  of  inorganic  and  organic 
substances,  as  the  radicle  CN,  or  cyanogen,  actually  ex- 
ists and  conducts  itself,  not  as  a  compound,  but  as  an  ele- 
mentary substance ;  and  if  all  organic  compounds  could 
be  shown  to  be  formed  of  compound  radicles,  this  would 
constitute  a  true  distinction  between  inorganic  and  or- 
ganic combinations.  But  this  is  not  the  case;  though 
some  chemists  have  theoretically  reduced  alcohol,  ether, 
acetic  acid,  and  in  fact  all  organic  vegetable  compounds, 
to  a  union  of  elements  with  compound  radicles,  these 
radicles,  unlike  cyanogen,  are  hypothetical.  It  is  said, 
for  example,  that  the  radicle  ethyl  (C2H5)  unites  with  oxy- 
gen to  form  the  oxide  of  ethyl  (€2115)20),  which  is  ether; 
but  ethyl  never  exists  in  nature  and  can  not  be  manufac- 
tured. The  same  is  true  of  the  radicles,  methyl,  acetyl, 
benzyl,  ammonium,  etc.  The  hypothetical  character  of 
these  radicles  is  universally  acknowledged,*  and  the  theory 

*  For  a  summary  of  the  history  of  these  so-called  organic  radicles  the  reader 
is  referred  to  a  lecture  by  M.  Auguste  Cahours,  published  by  the  "  Societe 
chimique  de  Paris,"  1S60,  p.  51. 


284  ORGANIC    NITROGENOUS    PRINCIPLES 

of  compound  organic  radicles,  although  it  may  serve  to 
exi)lain  the  composition  of  certain  classes  of  organic 
bodies,  is  not  universally  received  by  chemists  of  the  pres- 
ent day;  it  is  rather  a  mathematical  analysis  than  an 
actual  investigation  of  real  substances;  for  with  the  ex- 
ception of  one  or  two,  all  these  radicles  are  hypothetical. 
This  wholesale  assumption  of  imaginary  substances  vio- 
lates, in  toto,  the  axiom  enunciated  at  the  beginning 
of  this  article.  Instead  of  studying  the  behavior  of  or- 
ganic bodies,  phenomena  are  imagined  and  facts  distorted 
to  correspond  with  laws  which  are  known  to  regulate 
the  behavior  of  inorganic  substances.  But  it  is  beyond 
the  scope  of  this  paper  to  treat  of  these  purely  chemical 
questions;  and  the  reason  the  theory  of  organic  radicles 
has  been  discussed  at  all  is  that  it  was  followed  the  next 
year  (1838)  by  the  theory  of  Mulder,  by  which  he  at- 
tempted to  explain  the  constitution  of  the  albuminoids. 
He  supposed  all  organic  nitrogenous  substances  in  the 
body  to  be  formed  by  the  union  of  certain  elements  with 
a  radicle,  protein,  giving  to  them  the  name  of  protein  com- 
pounds. This  hypothesis  was  adopted  by  Liebig,  Dumas 
and  Simon  and  is  now  accepted  by  many  physiologists. 

Protein. — x^s  before  remarked,  the  only  albuminoids 
that  have  been  carefully  studied  are  fibrin,  albumin  and 
casein.  In  addition  to  a  great  similarity  in  the  general 
properties  of  these  substances,  ultimate  analysis  has  shown 
a  remarkable  likeness  in  chemical  composition.  It  is  not 
to  be  wondered  at,  then,  that  an  attempt  should  be  made 
to  reduce  all  the  compounds  of  this  class  to  a  series  derived 
from  a  common  radicle,  following  upon  the  theory  of  or- 
ganic vegetable  radicles.  This  was  done  by  Mulder;  who, 
treating  albumin,  fibrin  or  casein  with  alcohol  and  ether  to 
remove  fats  and  with  hydrochloric  acid  to  remove  inorganic 
salts,  dissolved  these  matters,  thus  purified,  in  a  solution 
of  potash  and  precipitated  by  acetic  acid  a  substance  said 
to  possess  always  the  same  characters,  which  he  called  the 
radicle  of  the  albuminoids,  and  which,  by  union  with  a  cer- 
tain quantity  of  sulphur  and  phosphorus,  was  capable  of 
forming  fibrin,  albumin  or  casein.  This,  which  is  merely 
an  extension  of  the  theory  of  compound  organic  radicles 
into  animal  chemistry,  has  a  more  plausible  basis  than  in 
the  case  of  vegetable  organic  compounds.     The  supposed 


ORGANIC    NITROGENOUS    PRINCIPLES  285 

radicle,  protein,  was  obtained  and  analyzed  by  Mulder;  and 
if  it  could  be  definitely  established  to  be  the  same  for  the 
various  substances  from  which  it  is  extracted,  and  if  these 
substances  could  be  shown  to  consist  always  of  this  radicle 
with  a  definite  proportion  of  sulphur  or  sulphur  and  phos- 
phorus, the  theory  would  be  sustained  so  far  as  possible 
with  present  means  of  investigation.  It  is  true  it  would 
be  sustained  only  by  analysis;  but  synthesis  has  not  yet 
been  applied  to  animal  chemistry.  But  the  protein  theory 
is  not  susceptible  of  analytical  demonstration.  The  com- 
position of  protein  itself  is  not  definitely  settled;  and  a  re- 
view of  the  methods  of  ultimate  organic  analysis  will  show 
that  the  varied  results  obtained  by  chemists  do  not  depend 
on  a  want  of  accurate  means  of  analysis  but  upon  the  in- 
definite characters  of  the  compounds  themselves.  Take, 
for  example,  the  analyses  of  Mulder  *  showing  the  com- 
position of  the  protein  groups,  and  compare  them  with  the 
results  obtained  by  other  chemists! 

Mulder  gives  the  following  formulas  for  the  protein 
group: 

C40H31N6O12  =  Protein. 

C4oH3iN50ia  +  SPhj  =  Fibrin  and  the  albumin  of  white  of  egg. 

C40H31N6O12  4-  SnPhi  =  Albunnin  of  serum. 

C40H31N5O12  +  S  =  Casein. 

These  analyses  by  Mulder  have  been  confirmed  by 
Schroder  and  Von  Laer.f 

Regnault  gives  as  the  constitution  of  protein  CseHo,- 
N,0,o;t  Sheerer,  Q.H^.Ni.Ox.;  *  Liebig,  C^HsoNeO^; 
and  Dumas,  C4sH33N0O17.ll 

The  composition  of  fibrin,  albumin  and  casein,  given  by 
Dalton  and  credited  to  Liebig,  is  as  follows:'^ 

Fibrin       =  C298H228N4o092S2 

Albumin  =  CoisHiegNovOeeSa 
Casein       =:  CaesHassNseOsoSa 

*  Robin  and  Verdeil,  "  Chimie  anatomique,"  tome  i.,  p.  652. 

f"  Animal  Chemistry  with  reference  to  the  Physiology  and  Pathology  of 
Man."     By  Dr.  J.  Franz  Simon.     Philadelphia,  1846. 

X  "  Cours  elementaire  de  chimie,"  etc.  Par  M.  V.  Regnault.  Paris,  1853, 
tome  iv.,  p.  114. 

*  Milne  Edwards,  "  Le9ons  sur  la  physiologie,"  etc.  Paris,  1857,  tome  i., 
p.  151. 

II  Robin  and  Verdeil,  o/>.  cit.,  tome  i.,  p.  651. 

^  Dalton,  "  Treatise  on  Human  Physiology'."  Second  edition.  Phila- 
delphia, 1861,  p.  80  ;  and  Robin  and  Verdeil,  op.  cit.,  tome  iii.,  p.  147. 


286  ORGANIC    NITROGENOUS    PRINCIPLES 

Denis,  in  a  paper  presented  to  the  Academy  of  Sciences 
at  Paris  in  1839.  advanced  the  view  that  fibrin  and  allnmiin 
are  identical  in  composition;  and  this  view  was  sustained 
by  Liebig  in  a  note  to  the  Academy  in  1841.* 

With  this  diversity  of  opinion  among  chemists,  based 
on  actual  analyses,  it  is  difficult  to  come  to  any  conclusion 
other  than  the  following: 

There  is  no  evidence  that  fibrin,  albumin  and  casein 
are  formed  by  the  union  of  a  definite  proportion  of  phos- 
phorus and  sulphur  with  a  common  radicle. 

In  addition  it  is  certain,  if  any  weight  is  to  be  attached 
to  ultimate  analyses,  that  the  properties  of  these  substances 
do  not  depend  entirely  on  their  chemical  composition.  Ac- 
cording to  the  analyses  of  Mulder,  even,  it  is  seen  that  two 
sul)stances  as  dissimilar  as  it  is  possible  for  substances  of 
this  class  to  be,  namely,  albumin  of  the  white  of  Qgg  and 
fibrin,  have  the  same  ultimate  composition.  The  ultimate 
composition,  then,  does  not  seem  to  be  important  as 
regards  the  general  properties  of  the  compound. 

Notwithstanding  all  the  labor  that  has  been  bestowed 
upon  the  ultimate  analysis  of  the  substances  under  consid- 
eration, the  question  of  their  composition  does  not  seem 
to  be  one  of  any  great  importance.  The  difficulties  of  such 
analyses  and  the  contradictory  results  in  the  hands  of 
skilful  chemists  show  that  a  knowledge  of  the  ultimate 
composition  of  organic  nitrogenous  substances  is  of  little 
value  as  a  means  of  distinguishing  them  from  each  other; 
and  such  analyses  throw  no  light  whatever  on  their  func- 
tion in  the  economy.  A  careful  review  of  the  facts  which 
have  been  accumulated  on  this  subject  leads  to  the  conclu- 
sion that  these  bodies  are  of  indefinite  chemical  composi- 
tion. In  the  first  place  they  are  not  crystallizable;  second, 
they  may  be  made  to  assume  different  forms  and  proper- 
ties by  the  action  of  imponderable  agents,  as  in  coagula- 
tion by  heat  or  galvanism,  without  losing  or  gaining  any 
elements;  third,  they  are  in  a  continual  state  of  change,  in 
nutrition  during  life,  without  losing  their  properties,  and 
will  continue  to  absorb  oxygen  and  exhale  carbonic  acid 
for  some  time  after  removal  from  the  body,+  and  shortly 

*  Robin  and  Verdeil,  o/>.  cii.,  tome  iii.,  p.  282. 

■f  G.  Liebig  has  shown  that  the  muscles  of  the  frog  will  continue  to  absorb 
oxygen  and  exhale  carbonic  acid  after  they  have  been  separated  from  the  body, 


ORGANIC    NITROGENOUS    PRINCIPLES  287 

after  these  properties  have  disappeared,  undergo  the 
changes  of  putrefaction;  finally,  there  is  no  great  differ- 
ence between  them  in  chemical  composition,  and  almost 
all  the  analyses  made  by  chemists  of  equal  skill  present 
great  variations.  Is  there  not,  then,  every  support  for  the 
assertion  that  their  chemical  composition  is  indefinite! 
Either  this  assertion  is  correct  or  the  methods  of  analysis 
employed  are  inaccurate.  As  so  much  depends  upon  this 
point,  I  venture  to  give  a  rapid  sketch  of  the  method  of 
analysis  most  commonly  employed  by  chemists. 

It  is  first  ascertained,  by  a  very  simple  process,  that  a 
given  substance,  as  albumin,  is  composed  of  certain  ele- 
ments, as  carbon,  hydrogen,  oxygen,  nitrogen,  sulphur  and 
phosphorus.  This  being  determined,  it  is  deprived  of 
moisture;  the  fat  is  removed  by  ether  and  alcohol;  and  the 
earthy  salts,  as  far  as  possible,  by  dilute  hydrochloric  acid. 
A  carefully  weighed  quantity  is  then  decomposed,  and  the 
proportions  of  these  elements  are  determined  in  the  follow- 
ing way : 

A  tube  of  the  hardest  glass,  half  an  inch  in  diameter, 
sixteen  to  eighteen  inches  long,  and  closed  in  a  flame  at 
one  end,  is  used  for  the  decomposition,  which  is  effected 
by  combustion.  The  oxidation  is  effected  by  means  of  the 
black  oxide. of  copper,  which  is  prepared  for  the  purpose 
perfectly  pure,  carefully  powdered  and  completely  freed 
from  moisture.  The  tube  is  first  filled  for  two  or  three 
inches  with  pure  oxide  of  copper.  The  organic  matter  is 
now  to  be  carefully  powdered,  incorporated  with  oxide  of 
copper  (it  is  best  to  employ  five  to  eight  grains  of  organic 
matter  for  the  analysis),  taking  care  that  none  is  lost,  and 
the  mixture  is  introduced  into  the  tube.  The  tube  is  now 
to  be  filled  to  within  an  inch  of  its  extremity  with  pure 
oxide  of  copper. 

In  this  part  of  the  manipulation,  care  should  be  taken 
to  remove  all  moisture,  as  this  would  affect  the  quantity 
of  hydrogen  obtained  from  the  combustion.  This  may  be 
done  by  attaching  the  tube,  after  it  has  been  filled,  to  one 
opening  of  a  small  airpump,  such  as  is  used  for  this  pur- 
pose, the  other  being  fitted  to  a  bent  tube  filled  with  pumice 
stone  and  sulphuric  acid.     By  placing  the  combustion  tube 

so  long  as  they  retain  their  contractility.  Lehmann,  "Physiological  Chem- 
istry," Philadelphia  edition,  vol.  ii.,  p.  474. 


288         ORGANIC   NITROGENOUS   PRINCIPLES 

in  a  long  dish  filled  with  warm  water  and  exhausting  the 
air  a  few  times,  all  the  moisture  may  be  removed. 

As  the  tube  is  to  be  subjected  to  intense  heat,  it  should 
be  wound  with  a  narrow  ribbon  of  sheet  brass,  which 
will  prevent  its  bending  when  it  becomes  softened.  There 
is  now  to  be  attached  to  the  open  end,  by  a  smaller  tube 
fitted  perfectly  with  a  cork,  a  light  tulnilar  apparatus  filled 
with  small  fragments  of  chloride  of  calcium,  the  tube  and 
its  contents  having  been  previously  weighed,  and  connect- 
ed with  this  is  a  series  of  bulbs,  called  Liebig's  potash  bulbs, 
partly  filled  with  a  solution  of  caustic  potash,  which  is  like- 
wise to  be  carefully  weighed.  The  heat  may  now  be  applied 
to  the  combustion  tube,  which  may  be  done  in  a  long  glass 
furnace  made  for  the  purpose,  or  by  surrounding  it,  well 
supported  in  a  long  iron  trough,  with  hot  coals.  The  heat  is 
applied  gradually,  beginning  at  the  nearer  end  of  the  com- 
bustion tube.  The  organic  substance  is  thus  completely  de- 
composed; and  if  it  is  composed  of  carbon,  hydrogen  and 
oxygen,  like  sugar,  the  analysis  will  be  complete,  this 
combustion  giving  the  carbon  and  hydrogen,  the  oxygen 
being  obtained  by  difTerence.  As  it  is,  all  the  hydrogen  is 
converted  into  watery  vapor,  which  is  absorbed  by  the 
chloride  of  calcium,  and  the  carbon,  converted  into  car- 
bonic acid,  is  absorbed  by  the  potash.  The  weight  of  these 
products  is  ascertained  by  taking  the  increase  of  weight  of 
the  calcium  tube  and  the  potash  bulbs,  and  the  quantities, 
of  carbon  and  hydrogen  are  deduced  therefrom. 

There  remain  now  the  nitrogen  and  sulphur.  The 
same  tube,  with  a  little  modification,  may  be  used  for  car- 
bon, hydrogen  and  nitrogen;  but  it  is  better  to  estimate  the 
nitrogen  in  another  apparatus.  For  this  purpose  a  com- 
bustion tube  is  used  similar  to  the  one  just  described,  pla- 
cing at  the  closed  end  a  few  grains  of  bicarbonate  of  soda; 
then  the  oxide  of  copper  as  before;  next  the  mixture  of 
oxide  of  copper  and  the  organic  matter;  next  another  layer 
of  pure  oxide  of  copper,  and  last  of  all  a  layer  of  pure  cop- 
per reduced  by  hydrogen.  The  extremity  is  then  con- 
nected with  one  opening  of  the  airpump,  and  to  the  other 
is  adapted  a  tube  which  opens  under  a  receiver  containing 
mercury  with  a  solution  of  potash  floating  on  the  top.  The 
air  is  then  exhausted  as  completely  as  possible  and  the  com- 
bustion tube  is  connected  with  the  receiver  by  opening  both 


ORGANIC    NITROGENOUS    PRINCIPLES  289 

stopcocks  of  the  airpump.  It  is  necessary  now  to  drive 
out  all  the  air  from  the  apparatus,  to  collect  the  pure  nitro- 
gen in  a  gaseous  form.  For  this  purpose  heat  is  applied  to 
the  farther  extremity  of  the  tube,  which  decomposes  the 
bicarbonate  and  carbonic  acid  gas  is  evolved.  It  can  be 
seen  that  all  the  air  is  driven  off,  by  the  complete  absorption 
of  the  gas  evolved  by  the  potash  in  the  receiver,  showing 
that  pure  carbonic  acid  is  coming  over.  Another  receiver 
filled  with  mercury  and  a  solution  of  potash  is  then  substi- 
tuted, the  heat  from  the  bicarbonate  is  withdrawn  and 
applied  gradually  from  the  anterior  portion  of  the  tube  as 
before.  Combustion  of  the  organic  matter  takes  place, 
which  results  in  watery  vapor,  carbonic  acid,  which  is  ab- 
sorbed by  the  potash  in  the  receiver,  and  nitrogen,  which 
passes  over  and  is  collected  in  a  gaseous  form.  Some  of 
the  nitrogen  is  oxidized  by  this  combustion,  but  as  it  passes 
over  the  hot  metallic  copper  in  the  nearer  extremity  of  the 
tube,  the  oxygen  is  retained  and  the  nitrogen  passes  over 
pure.  After  the  combustion  of  the  organic  matter  is  com- 
plete, heat  is  again  applied  to  the  bicarl:)onate  of  soda  so 
as  to  drive  ofif  what  nitrogen  remains  in  the  tube,  by  the 
evolution  of  carbonic  acid.  It  remains  now  to  remove  the 
receiver,  substitute  water  for  the  mercury,  measure  the  vol- 
ume of  the  gas,  taking  the  temperature  carefully  and  bring- 
ing the  level  of  the  water  in  the  tube  to  that  of  the  sur- 
rounding liquid,  and  thence  deduce  its  weight,  which  gives 
the  proportion  of  nitrogen. 

The  sulphur  and  phosphorus,  if  there  is  any,  exist  in 
very  small  quantity.  They  may  be  estimated  in  the  albu- 
minoids without  any  great  difficulty,  by  causing  them  to 
unite  with  soda,  as  sulphuric  or  phosphoric  acid,  and  then 
precipitating  with  the  chloride  of  barium  for  the  sulphur, 
and  by  a  process  a  little  more  complicated,  but  not  less 
exact,  for  the  phosphorus,  which  it  is  not  necessary  to  de- 
scribe here. 

In  this  manner  are  obtained  the  weights,  in  a  given 
portion  of  albumin,  of  all  its  ingredients  but  the  oxygen; 
viz.,  carbon,  hydrogen,  nitrogen  and  sulphur.  Subtract- 
ing the  sum  of  the  weights  of  these  substances  from  the 
whole  weight,  gives  the  oxygen;  and  reducing  to  100  parts 
gives  the  ultimate  composition. 

I  have  given  the  process  rather  fully,  to  show  how,  with 


290         ORGANIC    NITROGENOUS   PRINCIPLES 

certain  precautions,  in  the  hands  of  one  skilled  in  chemical 
manii)n]ati()ns,  it  may  be  made  as  accurate  as  any  operation 
in  inorj^anic  chemistry.  With  a  balance  that  will  turn  with 
less  than  y^Vs  of  a  gramme,  and  with  care  to  avoid  mois- 
ture, etc.,  in  the  apparatus,  the  result  should  be  always  the 
same,  if  the  substance  analyzed  had  always  the  same  com- 
position. 

The  next  step  is  to  establish  the  formula  in  equivalents. 
If  the  substance  used  is  an  acid  or  a  base  which  combines 
wath  any  substance  of  known  combining  equivalent,  this 
could  be  easily  done,  by  getting  the  weight  of  a  combining 
atom  by  experiment,  calculating  the  proportions  of  its  in- 
gredients to  this  weight,  and  dividing  the  quantity  of  each 
element  thus  obtained  by  its  combining  equivalent.  But 
in  the  case  of  the  albuminoids,  which  are  neutral,  this  can 
not  be  done.  A  formula  is  calculated  for  them  which  ex- 
presses the  elements  in  the  simplest  manner  so  as  to  give 
no  fractions,  generally  giving  an  even  number  for  the 
atoms  of  carbon.  Thus  Liebig  gives  as  the  formula  for 
fibrin,  Co98H228N4o092Si2.* 

This  review  of  the  mode  of  ultimate  analysis  of  organic 
nitrogenous  bodies  makes  it  evident  to  one  conversant 
with  chemical  manipulations,  that  the  contradictory  results 
obtained  by  different  chemists  are  not  due  to  imperfections 
in  the  analytical  process;  indeed,  the  process  is  acknowl- 
edged by  chemists  generally  to  be  as  accurate  as  that  for 
the  determination  of  the  composition  of  inorganic  sub- 
stances. The  only  way,  then,  to  explain  the  contradictory 
results  obtained  by  dififerent  chemists  of  equal  skill  and 
reputation,  is  to  assume  that  the  chemical  composition  of 
the  principles  is  indefinite.  While  enough  has  been  said, 
perhaps,  to  convince  the  reader  of  this,  it  follows  that  im- 
portant results  are  to  be  expected  rather  from  a  study  of  the 
condition  and  behavior  of  these  substances  in  the  economy 
than  their  decomposition  into  elements.  When  they  have 
been  extracted  from  the  bodv.  they  are  bv  no  means  in  the 
condition  under  which  they  normally  exist.     This  being 

*  It  is  hoped  that  the  reader  of  this  article  will  remember  that  it  was  writ- 
ten in  1863,  when  physiological  chemistry  was  in  its  infancy.  I  have  preferred 
to  publish  the  part  relating  to  organic  chemistry  as  it  first  appeared,  correcting 
only  a  few  of  the  formulas,  rather  than  attempt  to  adapt  it  to  modern  ideas  or 
omit  it  entirely. 


ORGANIC    NITROGENOUS    PRINCIPLES  291 

the  case,  it  is  for  the  physiological  chemist  to  give  their 
quantity,  properties,  etc.,  so  far  as  he  can,  in  the  condition 
in  which  they  really  exist  in  life;  the  physiologist  then  takes 
them  and  studies  the  phenomena  in  which  they  are  con- 
cerned. Here  comes  the  important  question:  What  is  the 
condition  of  existence  of  the  organic  nitrogenous  elements 
in  the  body?  On  the  answer  to  this  question  depends  the 
mode  of  proximate  analysis  of  the  organized  fluids  of  the 
body,  especially  the  blood,  which  is  all  important  to  the 
physiologist. 

Condition  of  Existence  of  Organic  Nitrogenous 
Substances  in  the  Body. — In  the  ordinary  proximate 
analysis  of  the  blood,  by  wdiich  is  meant  an  analysis  giving 
the  proportions  of  proximate  principles  without  any  refer- 
ence to  their  ultimate  composition,  the  albumin  and  fil^rin 
are  put  down  in  very  small  proportions.  Fibrin  is  recog- 
nized by  its  spontaneous  coagulability,  and  albumin,  by  its 
coagulability  by  heat  and  nitric  acid;  and  it  is  evident  that 
fibrin  may  be  extracted  from  the  blood  coagulated  on 
rods,  and  the  albumin  of  the  serum  solidified  by  heat  or 
nitric  acid,  in  quantities  which  are  much  greater  than  those 
given  in  analyses.  The  physician  finds  it  difificult  to  recon- 
cile to  his  ideas  of  albumin  and  fibrin  of  the  blood,  the  pro- 
portions of  sixty  to  sixty-five  parts  per  thousand  for  albu- 
min, and  two  and  a  half  for  fibrin.  The  reason  why  the  esti- 
mates fall  so  far  below^  our  ideas  is  that  chemists  never 
have  estimated  the  fibrin  and  albumin  as  they  are  separated 
from  the  fluids  by  coagulation,  which  changes  only  their 
form  and  not  their  weight,  but  after  separating  them  in 
this  way,  have  subjected  them  to  perfect  desiccation.  They 
have  given,  therefore,  not  the  weight  of  the  principles  as 
they  exist,  not  the  fibrin  and  albumin  in  a  condition  to 
nourish  the  body,  but  the  desiccated  substance,  altered, 
and  its  properties  destroyed  by  this  process.  Physiologists 
assume  that  fibrin  and  albumin  are  in  solution  in  the  water 
of  the  blood,  and  that  their  natural  condition,  in  a  state  of 
purity,  is  that  of  a  dry  powder.  In  this  case  it  is  extremely 
difficult  to  reduce  these  substances  to  their  natural  condi- 
tion. When  coagulated,  which,  according  to  this  view,  is 
a  precipitation,  a  large  quantity  of  water  persistently  re- 
mains, which  it  is  very  difficult  to  get  rid  of;  and  when  got 
rid  of,  the  dry  substance  must  be  weighed  quickly  and  with 


292  ORGANIC    NITROGENOUS    PRINCIPLES 

many  precautions  to  avoid  absorption  of  moisture.  Other 
matters  are  also  found  combined  with  coagulated  organic 
matters.  All  the  salts  found  in  the  blood  are  united  with 
them  as  well  as  water;  and  in  the  proximate  analyses,  these 
salts  are  generally  not  sei)arated  from  the  organic  substance 
before  it  is  weighed.  This  view,  which  is  almost  universally 
held  by  physiologists,  is  the  one  which  has  guided  all  the 
analyses  of  the  organized  fluids.  Of  the  original  works  to 
which  I  have  access,  that  of  Robin  and  Yerdeil,  on  "  Ana- 
tomical Chemistry,"  *  is  the  only  one  in  which  I  find  any 
dissent  from  the  prevailing  doctrine.  They  regard  the  or- 
ganic elements  of  the  fluids  as  naturally  liquid  and  not  in 
solution;  those  of  the  semisolids  as  naturally  semisolid; 
and  of  the  solids  as  solid.  The  contrary  view  seems  to  me 
radically  and  entirely  wrong;  and  all  analyses  of  the  organ- 
ized fluids,  made  under  the  idea  that  organic  substances  are 
in  solution,  fail  to  give  anything  like  a  correct  notion  of  the 
properties  of  these  substances.  The  analyses  of  the  blood 
which  are  embodied  in  the  latter  part  of  this  paper  are  the 
only  ones,  so  far  as  I  know,  which  have  been  attempted 
wnth  reference  to  the  real  condition,  as  it  seems  to  me,  of 
the  organic  constituents.  They  have  been  made  on  the 
following  principle: 

The  water  which  is  contained  in  coagulated  organic 
substances  and  which  may  be  driven  ofT  by  dry  heat  is  not 
part  of  the  water  which  held  the  organic  matter  in  solution, 
but  an  actual  constituent  of  the  substance,  as  much  as  car- 
bon, hydrogen  or  nitrogen,  and  is  indispensable  to  the 
properties  by  which  it  is  recognized  as  an  organic  principle. 

It  has  already  been  shown  that  ultimate  analysis  does 
not  give  an  idea  of  the  distinctive  characters  of  different 
organic  matters.  This  depends  upon  certain  characters 
which  are  found  in  all  principles  of  this  class,  and  further, 
upon  certain  properties  which  serve  to  distinguish  them 
one  from  another;  and  when  deprived  of  their  w^ater  of 
composition  by  desiccation,  neither  in  their  general  prop- 
erties nor  in  chemical  composition  are  there  any  means  of 
recognizing  them,  unless  it  is  bv  their  indefinite  chemical 
composition  and  the  impossibility  of  making  them  assume 
a  definite  or  crystalline  form. 

*  Op.  cit.,  tome  iii.,  p.  I2i. 


ORGANIC    NITROGENOUS    PRINCIPLES  293 

First,  in  regard  to  their  general  properties!  They  all 
undergo  a  change  peculiar  to  themselves,  called  putrefac- 
tion. This  property,  which  is  the  one  perhaps  most  dis- 
tinctive of  organic  matters,  disappears  when  they  are  de- 
prived, even  partially,  of  water;  a  fact  that  is  well  known 
and  of  which  there  is  a  familiar  example  in  the  preservation 
of  meats.  Again,  when  an  organic  substance  is  in  a  state 
of  putrefaction,  it  is  capable  of  inducing  the  same  change 
in  other  elements  of  this  class,  by  what  is  called  catalysis, 
or  acting  as  a  ferment.  As  water  is  necessary  to  putrefac- 
tion, it  consequently  is  necessary  to  the  development  of 
this  property.  Principles  of  this  class  also  undergo  a 
change  peculiar  to  themselves  in  cooking,  which  is  char- 
acterized by  the  development  of  volatile  empyreumatic 
substances.  Water  is  necessary  to  this  change,  for  if  ex- 
posed to  heat  after  water  has  been  driven  off,  as  has  already 
been  seen  in  the  study  of  the  method  of  ultimate  analysis, 
they  are  resolved  into  their  elements  without  undergoing 
any  such  change.  They  also  are  capable  of  regaining  their 
water  of  composition  after  desiccation,  possessing  to  an 
eminent  degree  what  is  called  the  property  of  hygrome- 
tricity,  by  which  they  are  returned  to  the  condition  they 
assumed  when  first  coagulated.  This  coagulability  is  also  a 
peculiar  property,  entirely  different  from  precipitation  from 
a  solution.  They  can  not  be  redissolved  in  the  liquid  from 
which  they  are  separated  by  coagulation.  For  example, 
all  of  them,  including  albumin,  are  insoluble  in  alcohol; 
but  if  albumin  is  coagulated  by  alcohol  and  afterward  freed 
from  it,  it  can  not  be  redissolved  by  pure  water  or  by  the 
liquid  from  which  it  was  separated.  When  once  coagulated 
they  have  undergone  a  change  and  can  not  be  redissolved 
except  by  means  which  change  them  still  more.  When 
they  have  been  coagulated  and  dried,  reduced  to  what  is 
called  a  condition  of  purity,  they  can  not  be  redissolved  and 
detected  by  their  property  of  coagulation;  for  they  are 
changed  and  consequently  are  not  in  their  natural  condi- 
tion. 

Fibrin  may  be  described  as  an  organic  constituent  of 
the  blood,  which  possesses  the  propertv  of  coagulating 
when  removed  from  the  body,  giving  this  property  to  the 
whole  mass  of  blood,  which  separates  after  a  time  into 
clot  and  serum.     Albumin  may  be  described  as  a  principle 


294  ORGANIC    NITROGENOUS    PRINCIPLES 

of  the  same  class,  existing  in  the  serum,  which  is  coagulated 
])}■  heat  or  nitric  acid.  These  are  naturally  lluid,  but  coagu- 
late, in  the  one  instance  spontaneously,  and  in  the  other, 
by  the  means  just  mentioned.  It  can  not  be  said  that  they 
are  principles  composed  of  so  many  atoms  of  carbon,  nitro- 
gen, etc.,  because  their  comi)osition  is  indefinite.  As  re- 
gards the  proportion  of  these  principles  contained  in  the 
blood,  one  can  say  only  that  after  they  have  been  separated 
from  this  fluid  and  after  all  their  water  has  been  driven  off, 
there  have  been  found  2^  parts  of  fibrin,  and  60  or  70  of 
albumin  per  i.ooo.  This  conveys  little  idea  of  the  real 
quantity,  but  only  the  quantity  of  anhydrous  matter  con- 
tained in  these  substances,  not  the  quantity  of  coagulating 
fibrin  and  albumin  found  in  the  blood.  Analyses  giving 
the  quantities  of  these  substances  as  nearly  as  possible  in 
their  natural  condition  have  never  been  made;  although 
they  would  seem  the  only  ones  that  could  convey  any 
definite  idea  of  what  is  most  important  to  know.  I  have 
attempted  to  supply  this  deficiency,  to  a  certain  extent,  in 
Part  II.,  on  the  Analysis  of  the  Blood. 

I  have  enumerated  nearly  all  the  properties  by  which 
one  can  recognize  organic  nitrogenous  substances,  sepa- 
rated from  the  living  organism,  as  a  class;  namely,  putre- 
faction, the  property  of  becoming  ferments,  changes  in 
coction,  desiccation,  hygrometricity  and  coagulation;  and 
all  of  these  depend  on  the  presence  of  water.  Should  it  not, 
then,  be  almost  conclusive  from  these  facts  that  water  is 
a  necessary  and  very  important  element  in  their  constitu- 
tion! It  is  true  that  it  is  separated  with  great  facility,  and 
that  its  union  wath  the  other  constituents  is  not  very  pow- 
erful; but  this  is  no  argument  against  the  fact  of  its  being 
in  a  condition  of  actual  union.  There  are  many  substances 
in  the  inorganic  world  which  have  a  union  no  more  power- 
ful than  that  of  water  in  organic  matters.  Take  the  single 
example  of  the  bicarbonate  of  soda.  The  second  equiva- 
lent of  carbonic  acid  is  driven  off  by  gentle  heat  and  even 
by  exposure  to  the  air  at  the  ordinary  temperature,  leaving 
the  salt  in  the  condition  of  a  carbonate. 

There  is  another  circumstance  in  connection  with  the 
mode  of  union  of  water  with  other  ingredients  to  form  an 
organic  body  which  serves  to  distinguish  it  from  mere 
solution.     When  a  solid  substance,  as  a  salt,  is  in  solution 


ORGANIC    NITROGENOUS    PRINCIPLES  295 

in  any  liquid,  it  requires  a  certain  quantity  of  the  liquid  to 
dissolve  a  certain  quantity  of  the  solid;  but  beyond  this  the 
liquid  may  be  increased  indefinitely,  the  solid  having  the 
same  relation  of  solution  to  the  whole  mass.  On  the  con- 
trary, when  one  chemical  compound,  as  nitric  acid,  unites 
with  another,  as  with  soda,  one  equivalent  of  the  one 
combines  with  one  equivalent  of  the  other,  and  if  more 
of  either  one  is  added,  it  does  not  enter  into  combination. 
I  regard  the  organic  substances  found  in  the  liquids  of 
the  body  as  naturally  liquid  and  mixed  with  the  other 
liquids;  the  water  which  enters  into  their  composition,  as 
represented  by  the  water  which  they  contain  when  sepa- 
rated from  the  other  liquids  by  coagulation;  and  this  quan- 
tity of  water,  though  not  absolutely  definite,  is  as  definite 
in  its  proportion  as  are  the  other  ingredients.  It  is  re- 
stricted within  definite  limits;  and  although,  w'hen  liquid, 
like  many  other  liquids  it  may  be  mixed  with  an  indefinite 
quantity  of  water,  when  separated  by  coagulation,  water 
will  always  be  found  in  about  the  same  proportion. 

There  is  another  point  of  view,  by  far  the  most  impor- 
tant physiologically,  from  which  to  study  this  question  of 
the  natural  condition  of  the  organic  constituents  of  the 
liquids.  Do  they  conduct  themselves  in  the  processes  of 
nutrition  like  the  inorganic  substances,  which  are  undoubt- 
edly held  in  solution,  or  like  substances  naturally  liquid? 

This  question  seems  to  me  very  easily  answered.  The 
processes  of  nutrition  of  the  organic  constituents  of  the 
body  consist  in  a  change  of  the  liquid  organic  substances, 
principally  the  albumin  and  fibrin,  into  those  which  are 
semisolid  and  solid,  like  myosin,  ossein,  etc.  In  the  proc- 
ess of  these  changes,  water  is  of  course  absolutely  neces- 
sary, and  is  deposited  with  the  other  constituents  of  the 
organic  matters.  It,  as  well  as  the  carbon,  hydrogen  and 
nitrogen,  is  necessary  to  the  constitution  of  the  myosin 
and  ossein  and  is  involved  in  all  the  changes  incident  to 
nutrition. 

Having  special  reference  to  the  blood  and  the  organic 
substances  which  it  contains,  the  relations  between  this 
fluid  and  the  tissues  constitute  one  of  the  most  important 
and  interesting  of  physiological  inquiries.  In  the  organic 
constituents  of  the  solids  and  semisolids  of  the  body  reside, 
undoubtedly,  the  vital  properties  which  lead  them  to  regen- 


296  ORGANIC    NITROGENOUS    PRINCIPLES 

erate  themselves  at  the  expense  of  the  circulating  fluid; 
and  in  the  tissues  and  organs,  as  well  as  in  the  blood,  the 
organic  matters  are  always  united  with  inorganic  salts,  as 
well  as  with  water.  Of  these  salts,  some,  in  connection 
with  organic  matter,  go  in  great  measure  to  make  up  the 
tissues,  as  the  phosphate  of  lime  in  the  bones;  wiiile  others 
seem  by  their  ])rcsence  to  regulate  the  nutritive  processes, 
like  the  chloride  of  sodium,  wdiich  is  more  abundant  in 
the  blood  than  in  the  tissues.  Organic  nitrogenous  mat- 
ters, whether  fluid,  semisolid  or  solid,  never  exist  alone, 
but  always  in  combination  with  inorganic  substances. 
It  is  impossible,  indeed,  in  extracting  the  organic  sub- 
stances from  the  body,  to  free  them  entirely  from  inorganic 
salts;  and  the  fibrin  and  albumin  of  the  blood  I  have  found 
to  contain  all  of  the  salts  which  exist  in  that  fluid.  The 
blood  contains  all  of  the  elements,  both  organic  and  inor- 
ganic, which  are  necessary  for  the  regeneration  of  the  tis- 
sues. The  inorganic  elements  are  deposited  unchanged, 
and  in  the  organic  elements  alone  resides  that  property 
of  mutual  convertibility  which  forms  myosin,  chondrin, 
ossein,  etc.,  out  of  albumin  and  fibrin.  In  this  process 
of  change  there  is  a  deposition  of  the  salts,  which  can 
not  take  place  by  itself  but  must  be  involved  in  the  deposi- 
tion of  organic  matter.  This  process  is  not  to  be  explained 
by  the  laws  of  chemical  attraction  or  represented  by  a 
change  in  chemical  formulas.  It  takes  place  only  in  organic 
living  bodies;  and  the  more  we  attempt  to  elucidate  it  by 
investigations  of  a  purely  chemical  nature,  the  farther  we 
remove  ourselves  from  a  comprehension  of  the  essence  of 
nutrition.  We  must  learn  to  look  on  processes  like  this 
as  physiological  and  not  chemical;  and  as  we  never  have 
constructed,  and  perhaps  never  shall  construct,  a  single  or- 
ganic nutritive  substance  out  of  its  elements,  or  changed 
one  into  another,  so  we  shall  ever  fail  to  comprehend  the 
phenomena  of  change  and  the  mystery  of  their  construction 
in  the  body,  if  we  persist  in  endeavoring  to  adapt  these 
phenomena  to  the  laws  which  regulate  the  composition  and 
changes  of  inorganic  substances.  When  w^e  study  the  com- 
position of  these  substances,  we  should  take  them  as  we 
find  them,  and  not  try  to  reduce  them  to  a  condition  ap- 
proximating that  of  minerals.  The  absence  of  useful  results 
following  the  labors  in  this  direction  of  so  manv  chemists 


ORGANIC   NITROGENOUS   PRINCIPLES  297 

should  be  a  warning  to  us  to  leave  the  beaten  track.  When 
we  study  their  properties,  we  have  already  seen  that  it  is 
necessary  to  take  them  as  they  are,  combined  with  water, 
•or  these  properties  are  lost.  When  we  come  finally  to  study 
their  functions  in  the  economy,  we  find  that  they  not 
only  contain  water,  but  inorganic  substances,  which  are  in- 
dispensable to  the  great  function  of  nutrition,  and  which 
can  not  be  separated  from  the  organic.  We  must  in  this 
study  recognize  the  following  important  facts: 

First.  Organic  nitrogenous  substances  are  the  only  ele- 
ments of  the  body  in  which  reside  the  properties  of  destruc- 
tion and  regeneration  during  life.  Fats,  sugars,  and  inor- 
ganic salts  operate  with  them,  and  by  virtue  of  this  prop- 
erty. 

Second.  They  are  of  indefinite  chemical  composition; 
and  no  great  physiological  importance  is  to  be  attached 
to  ultimate  analyses.  They  are  unstable,  in  a  state  of  con- 
tinual change  during  life  and  soon  alter  after  death  or  after 
removal  from  the  body. 

Third.  They  assume  the  consistence  of  the  tissue  or 
fluid  in  which  they  exist.  They  are  solid  in  the  solids,  like 
bone;  semisoHd  in  the  semisolids,  like  muscle;  liquid  in  the 
liquids,  like  the  blood.  They  are  not  dissolved  in  water, 
but  water  is  an  ingredient,  and  its  quantity  determines 
their  consistence. 

Fourth.  In  the  body  they  never  exist  alone,  but  are 
always  combined  with  inorganic  substances,  which  accom- 
pany them  in  the  changes  which  they  undergo  in  the  proc- 
esses of  nutrition  and  disassimilation. 

Fifth.  As  all  the  proximate  analyses  of  the  organized 
fluids,  particularly  the  blood,  have  been  made  with  the  idea 
that  the  organic  ingredients  were  solids  in  solution  in 
water,  these  quantitative  analyses  give,  not  the  propor- 
tions of  fibrin  or  albumin,  but  dried  fibrin  and  albumin, 
the  original  substance  subjected  to  a  process  which  drives 
ofif  its  most  important  constituent  and  which  alters  its 
properties.  Such  analyses,  as  representing  real  quantities, 
.are  erroneous. 


298         ORGANIC    NITROGENOUS   PRINCIPLES 


PART   II 

Analyses  of  the  Blood  with  Reference  to  its 
Organic  Constituents. — From  the  review  just  given  of 
the  organic  constituents  of  the  body  and  the  intimate  rela- 
tion seen  to  exist  between  the  tissues  and  the  blood,  it 
is  evident  that  an  analysis  of  the  nutritive  fluid,  espe- 
cially with  reference  to  its  organic  constituents,  is  of  great 
interest  and  importance.  This  has  long  been  recognized; 
and  in  late  years  a  great  part  of  the  labors  of  investigators 
in  physiological  chemistry  have  been  devoted  to  this  sub- 
ject. It  is  not  my  purpose  here  to  consider  any  but  the 
organic  principles  of  the  blood.  The  constitution  of  this 
fluid,  in  its  entire  physiological  and  pathological  relations, 
is  too  extended  ^  theme  to  be  considered  in  this  place. 
The  fact  that  the  blood  contains  certain  excrementitious 
substances  shows  that  this  fluid  is  connected  with  the  waste 
as  well  as  the  repair  of  the  system.  The  pathological  im- 
portance of  this  has  been  settled  experimentally  by  the  dis- 
covery of  the  accumulation  of  excrementitious  matters  in 
the  circulating  fluid,  giving  rise  to  certain  pathological  con- 
ditions; as  for  example,  urea,  producing  a  condition  of 
the  system  known  under  the  name  of  uremia;  and  more 
lately,  the  discovery  of  the  character  of  cholesterin  as  an 
excretion  and  its  accumulation  in  the  blood,  under  cer- 
tain conditions  of  the  liver,  constituting  cholesteremia.* 
These  are  only  two  examples  where  diseased  conditions  of 
the  system  have  been  clearlv  shown  to  depend  upon  the 
accumulation  of  a  specific  excrementitious  substance  in  the 
blood;  but  the  work  in  this  direction  is  but  begun;  and 
I  venture  to  predict  that  more  light  will  be  thrown  on 
pathology  by  the  discovery  of  new  toxins  in  the  blood, 
dependent  on  defective  excretion,  than  by  any  other  line 
of  experimental  inquiry. 

The  proximate  analyses  of  the  blood  up  to  this  time 
have  been  made  under  the  supposition  that  the  organic 
matters,  fibrin  and  albumin,  are  solid  matters  in  solution; 
but  according  to  the  \'iews  advanced  in  Part  I.;  namely, 
that  their  real  condition  is  one  of  fluidity,  and  that  when 

*  See  an  article  on  a  "  New  Excretory  Function   of  the   Liver,"  by  the 
author,  published  in  the  number  of  this  Journal  for  October,  1862. 


ORGANIC    NITROGENOUS    PRINCIPLES  299 

deprived  of  water  they  lose  one  of  their  most. important 
constituents,  this  mode  of  analysis  is  inadmissible.  The 
actual  quantities  of  fibrin  and  albumin  can  no  more  be  rep- 
resented by  the  residue  of  evaporation  than  by  the  residue 
of  calcination,  which  latter  would  leave  only  inorganic  mat- 
ter. Before  giving,  however,  the  processes  by  which  I 
have  attempted  to  estimate  the  c^uantities  of  undried  fibrin, 
albumin  and  globules  in  the  circulating  fluid,  I  shall  give 
a  rapid  review  of  the  methods  of  proximate  analysis  which 
are  now  generally  employed. 

Berzelius,  followed  soon  after  by  Marcet,  made  the 
first  extended  quantitative  analyses  of  the  blood.  He  ana- 
lyzed the  serum  of  human  blood  and  indicated  certain  quan- 
tities of  albumin,  lactate  of  soda,  muriate  of  soda,  etc.  He 
put  the  quantity  of  dried  albumin  at  80  parts  per  1,000, 
which  is  about  the  proportion  given  in  the  analyses  of  chem- 
ists of  the  present  day.  His  researches  w^ere  published  in 
1808  and  were  followed  by  the  analyses  of  Marcet,  in  181 1, 
which  gave  nearly  the  same  results.  In  1823  Prevost  and 
Dumas  published  their  researches  on  the  composition  of 
the  blood,  with  a  full  account  of  their  process.  This  proc- 
ess, with  slight  modifications,  is  the  one  employed  gener- 
ally at  the  present  time.  The  following  are  the  principal 
steps  in  the  analysis:  The  filjrin  is  separated  from  a  weighed 
quantity  of  blood  by  whipping  with  a  bundle  of  broom- 
corn,  carefully  collected,  dried  and  weighed.  Another 
specimen  of  blood  is  set  aside  to  coagulate,  and  after  it  has 
fully  separated  into  clot  and  serum,  the  clot  is  dried  and 
weighed;  the  proportion  of  fibrin  ascertained  from  the  first 
specimen  is  subtracted,  which  gives  the  quantity  of  dried 
globules.  The  serum  is  then  evaporated  to  dryness,  the 
residue  extracted  thoroughly  with  boiling  water,  e^her  and 
hot  alcohol,  to  remove  inorganic  salts  and  fats  and  af^^er- 
ward  weighed,  which  gives  the  proportion  of  albumin.  The 
fats  are  easily  extracted  with  ether;  and  the  inorganic  con- 
stituents are  estimated  after  incineration,  by  a  process 
which  it  is  not  necessar}^  to  descril:!e.  This  process  has 
been  followed,  with  unimportant  modifications,  by  a  num- 
ber of  chemists,  who  have  done  little  more,  in  regard  to  the 
albumin  and  fibrin,  than  confirm  the  observations  of  Pre- 
vost and  Dumas.  Among  these  may  be  mentioned  Andral 
and  Gavarret,  Becquerel  and  Rodier,  Sheerer,  and  Simon. 


300         ORGANIC    NITROGENOUS   PRINCIPLES 

Among  these  observers,  ])crhaps,  the  process  adopted  by 
Becqiierel  and  Rodier  is  one  as  generally  accepted  by 
physiologists  as  any,  and  I  shall  therefore  translate  from 
their  work,  entitled  "  Traite  de  chimie  pathologique,"  so 
much  of  it  as  refers  to  the  estimation  of  the  fibrin,  albumin 
and  globules: 

"  First  Series  of  Operations. — This  is  designed  to  furnish : 
First,  the  density  of  the  blood  and  that  of  the  serum;  second,  the 
weight  of  fibrin  and  globules  and  of  the  solid  matter  of  the  serum 
taken  as  a  whole.  These  processes  are  founded  on  the  same  prin- 
ciple which  served  as  the  basis  of  the  process  devised  long  since 
by  M.  Dumas.  We  suppose  that  all  the  water  contained  in  the 
blood  forms  part  of  the  serum  and  should  be  attributed  to  it.  Still, 
in  admitting  this  principle,  we  have  not  always  applied  it  in  the 
same  manner. 

"  The  following  is  our  mode  of  operation : 

"  We  practise  upon  the  person  whose  blood  we  wish  to  analyze, 
a  bleeding  of  about  375  grammes.  The  blood  which  first  flows 
from  the  vein  is  received  in  a  glass  vessel,  graduated  and  capable 
of  holding  about  125  cubic  centimetres  of  this  liquid.  We  collect  it 
and  whip  it  with  a  bundle  of  broomcorn.  We  thus  obtain  the 
fibrin,  which  we  must  wash,  desiccate  and  weigh. 

"  The  blood,  thus  defibrinated,  is  then  put  aside  to  serve  for 
other  operations. 

"  The  blood  which  flows  from  the  vein,  after  these  125  cubic 
centimetres,  is  collected  with  care  in  a  vessel  of  the  capacity  of  250 
to  300  cubic  centimetres  and  left  to  itself.  This  blood  coagulates, 
and  once  the  coagulation  effected,  we  separate  carefully  the  serum, 
which  we  put  aside  in  a  vessel ;  as  to  the  clot,  after  having  taken 
note  of  its  physical  characters,  we  may  set  it  aside. 

"  Let  us  see  now  what  we  do ;  first,  with  the  defibrinated  blood ; 
second,  with  the  serum. 

"  A.  The  defibrinated  blood  is  first  weighed  at  a  definite  tem- 
perature in  a  glass  specific-gravity  bottle.*  We  compare  then  the 
weight  which  we  obtain  in  this  operation  with  the  weight  of  the 
same  volume  of  distilled  water ;  and  we  thus  have,  by  a  very  sim- 
ple calculation  which  it  is  useless  to  reproduce  here,  the  exact 
weight  of  the  125  cubic  centimetres  of  blood  which  we  whipped  to 
separate  the  fibrin,  ana  consequently  the  weight  of  this  same  fibrin 
contained  in  i.ooo  grammes  of  blood.  Once  this  operation  effected, 
we  take  a  definite  quantity  of  defibrinated  blood,  which  we  weigh, 
which  we  desiccate,  which  we  afterward  weigh  anew,  and  we  thus 
have  the  weight  of  the  quantity  of  water  which  it  contains.  Let 
us  take,  for  example,  in  order  to  make  ourselves  better  vmderstood, 
arbitrary  numbers  which  we  shall  make  use  of  also  to  deduce  the 
weight  of  the  globules:  100  grammes  of  defibrinated  blood,  liquid, 

*  All  our  specific-gravities  were  taken  at  a  temperature  of  12°  (53.6°  Fahr.) 
and  compared  exactly  with  distilled  water  at  the  same  temperature. 


ORGANIC   NITROGENOUS   PRINCIPLES         301 

gives  20  parts  of  solid  material  and  80  parts  of  water.  Then  20 
parts,  thus  dried,  are  calcinated  to  give  us  the  inorganic  matters; 
we  shall  return  to  this. 

"  B.  The  serum. — After  having  determined  the  specific  gravity 
of  the  serum,  we  take  a  given  quantity  of  this  liquid  which  we 
weigh,  which  we  desiccate,  which  we  afterward  weigh  anew;  the 
difference  of  these  two  weights  gives  that  of  the  water;  as,  for  ex- 
ample, 100  grammes  of  liquid  serum  having  given  10  grammes  of 
solid  matter  and  90  grammes  of  water.  These  operations  termi- 
nated, we  possess  the  figures  necessary  to  deduce  the  weight  of  the 
globules  and  that  of  the  solid  matters  of  the  serum  contained  in  100 
grammes  of  defibrinated  blood.  Indeed,  as  all  the  water  of  the 
defibrinated  blood  should  be  attributed  to  the  serum,  we  must  make 
the  following  proportion : 

80  X  10         „ 

80  :  .r  : :  go  :  10  or  .r  = =  0.0  p;r. 

90 

"  This  proportion  8.8  represents  the  sum  of  the  solid  matters  of 
the  serum  contained  in  100  grammes  of  defibrinated  blood,  and  sub- 
tracting that  from  20,  the  weight  of  this  blood  desiccated,  we  have 
1 1.2  which  represents  the  weight  of  the  globules,  and  in  calculating 
the  whole  to  1,000,  v^'e  have  1,000  grammes  of  blood,  containing: 

Water 800  grammes. 

Globules 112 

Solid  matters  of  the  serum 88         " 

"  The  weight  of  the  fibrin  has  been  given  by  the  first  operation 
and  should  be  added.  Its  weight  is  so  small  in  proportion  to  1,000 
grammes  of  blood,  that  we  may  neglect  a  little  correction  which  we 
should  have  to  make  for  the  weight  of  the  fibrin  in  addition  to  the 
1,000  grammes  of  defibrinated  blood. 

"  Such  is  the  first  series  of  operations ;  for  the  second  we  shall 
make  use  of  the  dried  serum,  and  for  the  third,  of  the  defibrinated 
blood  calcinated. 

"  Second  Series  of  Operations. — These  operations  are  de- 
signed to  give  the  weight  of  the  extractive  matters  and  that  of  the 
fatty  matters.     The  following  is  our  mode  of  operation : 

"  The  serum,  having  been  dried  with  precaution  in  an  '  etuve,' 
and  pulverized  with  the  greatest  care,  is  treated  repeatedly  with 
boiling  water  until  this  water  has  completely  freed  it  from  every- 
thing which  it  can  dissolve.  These  last  are,  on  the  one  hand,  ex- 
tractive matters,  such  as  osmazome,  the  coloring  matter  of  serum, 
etc.,  etc.,  and  on  the  other  hand,  the  salts  which  are  in  solution  in 
the  serum  and  are  in  a  free  state. 

"  The  serum,  thus  extracted  with  water,  is  dried  again  and 
weighed,  the  difference  from  the  weight  obtained  by  the  first  weigh- 
ing indicates  that  of  the  matters  we  have  mentioned  and  which  the 
water  has  removed.  The  product  of  the  second  desiccation  is  then 
treated  with  boiling  alcohol  at  90°,  until  it  is  completely  extracted. 
The  insoluble  residue  is  pure  albumin,  of  which  we  may  take  the 
weight  after  having  dried  it.  As  to  the  boiling  alcohol,  it  holds 
in  solution  all  the  fatty  matters,  which  can  be  separated  by  em- 


302  ORGANIC    NITROGENOUS    PRINCIPLES 

ploying  the  process  indicated  by  M.  F.  Boudet,  and  of  which  we 
think  it  unnecessary  to  give  a  description.  It  gives  the  serolin, 
cholesterin  and  saponifiable  fats."  * 

The  above  qtiotation  is  a  fair  representation  of  the  mode 
of  analysis  most  commonly  made  use  of  at  the  present  day. 
It  differs,  however,  very  little  from  that  indicated  by  Du- 
mas. There  are  certain  objections  to  this  process,  aside 
from  those  which  have  reference  to  the  estimation  of  fibrin 
and  albumin,  which  have  long  engaged  more  or  less  the 
attention  of  physiological  chemists  and  are  acknowledged 
to  be  well  founded.  It  will  be  observed  that  all  the  water 
is  attributed  to  the  plasma,  while  the  globules  are  estimated 
dry.  This  is  manifestly  faulty,  as  the  most  cursory  micro- 
scopic examination  of  the  blood-globules  is  suf^cient  to 
show  that  they  have  a  consistence  dependent  upon  the 
presence  of  a  certain  quantity  of  water;  and  though  it  may 
be  convenient  to  estimate  these  bodies  dry,  such  an  esti- 
mate gives  no  idea  of  their  real  proportion.  This  was  ap- 
preciated as  long  ago  as  1828,  by  Denis,  who  attempted  to 
give  the  proportions  of  moist  globules  by  a  process  which 
had  avowedly  little  accuracy  and  which  he  afterward  aban- 
doned for  the  original  process  of  Dumas. f  In  1844 
Figuier  published  an  analysis  of  the  blood  which  gives 
an  estimate  of  the  moist  globtiles  by  a  process  that  I  have 
employed  in  the  analyses  which  follow,  and  which  seems 
to  me  to  give  sufficiently  accurate  results,  although  Denis 
does  not  consider  it  superior  to  his  own.  This  process  was 
accepted  by  Dumas  with  some  modifications  which  are  de- 
scribed by  him  in  the  "  Annales  de  chimie  et  de  physique  " 
for  1846,  p.  452.  The  process  of  Figuier  depends  on  the 
property  which  certain  saline  substances  have,  mixed  with 
the  blood,  of  retaining  the  globules  on  a  filter.  The  modi- 
fication by  Dumas  is  intended  to  avoid  a  difficulty  which 
sometimes  occurs  from  alteration  and  liquefaction  of  the 
globules,  by  which  some  pass  through  a  filter  and  are  lost. 
It  consists  in  passing  a  continuous  current  of  air  through 
the  filtering  fiuid,  which  prevents  this  change.  In  the  anal- 
yses I  have  made  I  have  not  found  it  necessary  to  adopt 
this  precaution. 

lerel  and  Rodier,  op.  cit.,  p.  21. 
[emoire  sur  le  sang."     Par  P.  S.  Denis  (de  Commercy).     Paris,  1859, 
P-  51. 


*  Becque 
t  "  Mem 


ORGANIC    NITROGENOUS    PRINCIPLES  303 

The  following  is  the  process  described  by  Figuier, 
translated  from  the  '*  Annales  de  chimie  et  de  physique."  * 
It  was  not  used  by  him  to  determine  the  proportion  of 
moist  globules;  the  globules  are  merely  separated  from  the 
blood,  dried  and  estimated  in  this  condition  Hke  the  other 
organic  matters. 

"  The  blood  furnished  by  a  venesection  is  whipped  on  its  dis- 
charge from  the  vein  according  to  the  process  of  IM.  Dumas.  The 
fibrin  separates  and  adheres  to  the  little  broomcorns.  The  liquid 
is  passed  through  a  fine  cloth  to  separate  that  portion  of  the  fibrin 
which  does  not  adhere  to  the  broom.  This  fibrin  is  then  washed 
in  a  current  of  water,  then  dried  in  a  water-bath,  and  weighed, 
after  having  been  treated,  if  desired,  with  ether  to  remove  a  little 
fatty  matter. 

"  In  taking  the  total  weight  of  the  blood  which  has  given  this 
quantity  of  fibrin,  we  shall  have  the  proportion  of  the  fibrin  to  the 
other  elements  of  blood. 

"  We  then  take  80  or  90  grammes  only  of  the  defibrinated  blood 
which  we  treat  with  about  twice  its  volume  of  a  solution  of  sulphate 
of  soda  marking  sixteen  to  eighteen  degrees  in  the  aerometer  of 
Baume,  and  this  is  thrown  on  a  half-filter  weighed  in  advance,  and 
previously  moistened  with  the  saline  solution ;  with  these  precau- 
tions the  serum  filters  quite  rapidly  with  a  yellowish  color. 

"  We  understand  that,  to  remove  from  the  globules  that  remain 
on  the  filter,  the  solution  of  sulphate  of  soda  with  which  they  are 
impregnated,  we  can  not  simply  wash  the  filter,  for  that  would  dis- 
solve a  portion  of  the  globules  and  the  fluid  would  pass  red  like 
the  blood.  But  a  property  peculiar  to  the  globules  allows  us,  hap- 
pily, to  surmount  this  difficulty.  When  they  are  heated  to  90°  Cent., 
as  Berzelius  has  already  seen,  the  globules  are  coagulated  entire, 
and  the  entire  mass  becomes  concrete  without  yielding  to  the  water 
any  of  the  organic  matter.  We  have  only,  then,  to  place  the  filter 
in  a  capsule  containing  boiling  water,  repeating  this  process  two  or 
three  times.  The  sulphate  of  soda  is  dissolved  and  the  water  takes 
almost  nothing  from  the  globules,  for  the  fluid  is  almost  colorless 
and  does  not  contain  any  organic  matter  appreciable  by  tannin  or 
corrosive  sublimate. 

"  To  separate  the  albumin  from  the  filtered  serum  it  suffices  to 
carry  it  to  the  point  of  ebullition  in  a  capsule.  The  albumin  coagu- 
lates ;  it  is  collected  in  a  little  net  of  fine  cloth ;  it  is  washed  and 
weighed,  after  having  been  dried,  by  the  water  bath.  Finally,  to 
determine  the  quantity  of  water  contained  in  the  blood,  we  take 
twenty  or  twenty-five  grammes  which  we  evaporate  to  dryness  in 
a  water  bath.  The  weight  of  the  residue  indicates  the  proportions 
of  water  and  solid  elements. 

*  "  Sur  une  methode  nouvelle  pour  I'analyse  de  sang,  et  sur  le  constitution 
chimique  des  globules  sanguins."  Par  M.  L.  Figuier. — "Ann.  de  chim.  et 
de  phys.,"  1844,  3""®  serie,  tome  xi.,  p.  506. 


304         ORGANIC   NITROGENOUS   PRINCIPLES 

"  The  soluble  salts  of  the  serum  are  represented  by  the  differ- 
ence of  the  weight  of  the  blood  employed  and  the  sum  of  the  albu- 
min, water,  fibrin  and  globules  determined  directly." 

The  above  is  a  very  simple  and  accurate  process  for  de- 
termining the  globules  and  organic  constituents  of  the 
blood,  but  according  to  the  view  already  indicated,  it  is 
open  to  the  same  objection  as  the  other,  as  it  gives  the 
quantity  of  these  ingredients  dried,  and  not  as  they  really 
exist. 

Schmidt,  of  Dorpat,  recognizing  the  necessity  of  a 
proper  estimate  of  the  moist  globules,  endeavored  to  estab- 
lish a  certain  proportion  of  water  to  be  constantly  attributed 
to  them;  so  that  by  adding  this  quantity  to  the  estimate  of 
the  dry  globules  by  Prevost  and  Dumas  and  others,  their 
results  could  be  made  use  of.  He  endeavored  to  do  this 
by  comparative  microscopic  measurements  of  the  moist 
and  dry  globules,  and  he  arrived  at  the  conclusion  that  the 
dry  globules  multiplied  by  four  would  give  the  cjuantity  of 
moist  globules.  Though  this  process  was  adopted  by  Leh- 
mann  as  the  most  accurate,  it  is  evident  that  it  can  not  pos- 
sibly be  exact;  especially  if  the  proportion  of  water  in  the 
globules  is  not  always  the  same,  as  is  stated  by  Zimmer- 
mann. 

Zimmermann  attempted  to  give  the  proportion  of  water 
in  the  globules  by  estimating  the  quantity  of  chlorides  in 
the  blood,  assuming,  with  Berzelius,  that  all  the  chlorides 
are  contained  in  the  serum  and  there  exist  none  in  the 
corpuscles.  He  estimated  first  the  proportion  of  the  chlo- 
rides in  the  serum,  then  the  quantity  of  chlorides  in  a 
given  quantity  of  blood,  whence  he  deduced  the  propor- 
tion of  serum  in  the  blood;  then  subtracting  the  water 
contained  in  the  serum  from  the  water  contained  in  the 
entire  blood,  he  obtained  the  proportion  of  water  in  the 
globules.  As  it  is  by  no  means  certain  that  the  blood- 
globules  contain  none  of  the  chlorides,  this  process  can 
not  be  accepted. 

Other  methods  of  a  very  complicated  character  have 
been  proposed  by  Vierordt,  Le  Canu  and  Lehmann,  which 
it  is  not  necessary  to  describe,  as  they  present  no  advan- 
tages over  the  foregoing. 

The  most  recent  process  that  has  been  proposed 
originated    with    Denis    and    was    published    by    him    in 


ORGANIC    NITROGENOUS    PRINCIPLES          305 

1859.*  His  manipulations  to  get  rid  of  the  interstitial 
serum  of  the  globules  are  complicated,  difficult  and  of 
questionable  efficacy.  He  arrives,  by  this  process,  at 
very  nearly  the  results  I  have  obtained  by  the  process 
of  Figuier,  which,  from  its  simplicity,  is  much  to  be 
preferred. 

From  this  brief  review  of  the  processes  for  the  analysis 
of  the  blood,  especially  with  reference  to  the  fibrin,  albu- 
min and  globules,  it  is  seen  that  no  analysis  has  ever  been 
made,  or  even  attempted,  which  would  give  the  real  quan- 
tities of  fibrin  and  albumin;  in  all  of  them  the  dry  residue, 
and  not  the  substance  itself,  is  given.  In  the  estimation 
of  the  globules,  however,  this  desiccating  process  is  so 
evidently  faulty  that  efforts  have  been  made  to  estimate 
them  in  their  moist  state,  or  as  they  really  exist.  As  yet 
there  is  no  one  process  for  arriving  at  this  end  that  is 
generally  accepted  by  physiological  chemists.  From  my 
own  observations  in  regard  to  all  the  constituents  under 
consideration,  it  seems  impossible  to  make  an  analysis 
which  will  be  perfectly  accurate;  but  absolute  accuracy  is 
not  indispensable.  One  can  get  near  enough  to  the  truth 
for  all  practical  purposes;  and  as  the  comparison  of  differ- 
ent analyses  made  in  the  same  w-ay  gives  them  much  of 
their  value,  it  is  best  to  fix  upon  that  process  for  estimation 
of  the  moist  globules  which  is  simplest  and  w-hich  seems 
to  give  the  most  reliable  results.  It  is  manifestly  better  to 
get  an  approximate  idea  of  the  fibrin,  albumin  and  globules 
of  the  blood  in  the  condition  in  which  they  really  exist  than 
to  take  the  quantity  of  dry  residue,  which  gives  no  idea 
whatsoever. 

Having  in  view,  then,  the  condition  of  existence  and 
functions  of  the  organic  constituents  of  the  blood,  it  is  only 
an  estimate  of  these  principles  in  a  moist  state  that  can 
give  any  clear  idea  of  their  proportions. 

Analytical  Process. — In  the  process  which  I  shall 
describe,  I  have  endeavored  to  simplify  manipulations  so 
far  as  is  consistent  with  reasonable  accuracy,  deeming  it 
important  to  put  such  investigations  within  the  reach  of 
every  one  rather  than  to  complicate  the  process  by  precau- 
tions which  are  designed  to  avoid  errors  so  slight  that  they 

*  Denis,  op.  cit. 


3o6  ORGANIC   NITROGENOUS    PRINCIPLES 

may  practically  be  disregarded.  T3umas  has  shown  that  the 
composition  of  the  blood  is  not  precisely  the  same  at  the 
beginning  and  the  end  of  a  bleeding;  and  he  recommends, 
therefore,  that  the  blood  be  drawn  in  ecpial  quantities  in 
four  vessels,  defibrinating  the  specimens  in  the  second  and 
third,  and  allowing  those  in  the  first  and  fourth  to  separate 
into  clot  and  serum.  By  comparing  the  results  of  the  sepa- 
rate analyses,  a  correction  may  be  made.  I  have  not  found 
it  necessary  to  use  more  than  two  specimens  of  two  to  four 
ounces  each;  and  with  this  quantity  such  a  precaution  is 
not  necessary. 

It  is  very  important  to  cover  the  vessels  which  contain 
the  blood  and  to  weigh  them  as  soon  as  possible;  for  the 
specimens  lose  weight  very  rapidly  by  evaporation,  as  has 
been  shown  by  Becquerel  and  Rodier,*  which  would  seri- 
ously interfere  with  the  quantitative  analysis. 

The  blood  to  be  analyzed  is  taken  from  the  arm  and 
received  into  two  carefully  weighed  vessels.  The  quantity 
in  each  vessel  may  be  two  to  four  ounces.  One  of  the  speci- 
mens is  whipped  with  a  small  bundle  of  broomcorn,  pre- 
viously moistened  and  weighed,  so  as  to  collect  the  fibrin; 
and  after  the  fibrin  is  completely  coagulated,  the  whole  is 
carefully  w^eighed,  deducting  the  w^eights  of  the  vessel  and 
broomcorn,  w'hich  gives  the  weight  of  the  specimen  of 
blood  used.  The  other  specimen  is  set  aside  to  coag- 
ulate. 

The  first  specimen  is  to  l)e  used  for  the  estimation  of 
fibrin  and  globules;  the  second  is  set  aside  to  coagulate 
and  is  used  to  estimate  the  albumin. 

The  first  specimen  of  blood  is  now^  passed  through  a 
fine  sieve  to  collect  any  fibrin  that  may  not  have  become 
attached  to  the  wisp;  the  fibrin  is  stripped  from  the  wasp 
and  washed  under  a  stream  of  water.  This  may  be  done 
very  rapidly  by  causing  the  water  to  flow  through  a  small 


*  In  experiments  by  Becquerel  and  Rodier  with  reference  to  the  loss  of 
weight  by  evaporation,  the  following  results  were  obtained.  The  blood  was 
drawn  into  a  porcelain  vessel  about  two  and  a  half  inches  in  diameter : 

Weight  of  blood  on  being       Weight  of  blood  2  'Weight  of  blood  24 

drawn  from  the  vein.  hours  after.  hours  after. 

1st  Exp 13-242  grammes         13-070  grammes         11. 510  grammes 

2d  Exp. .  .  .   14.905         "  14-727         "  I2.g77 

3d  Exp 22.453         "  22.308         "  20.337 

— "  Chimie  pathologique,"  p.  31. 


ORGANIC    NITROGENOUS    PRINCIPLES  307 

strainer,  so  as  to  break  it  up  into  a  number  of  little  streams, 
and  kneading  the  fibrin  in  the  fingers,  doing  this  over  a 
sieve  so  as  to  catch  any  particles  that  may  become  detached. 
In  this  way  it  may  be  freed  from  the  globules  in  five  or  ten 
minutes.  The  fibrin  thus  washed  is  then  freed  from  adher- 
ent moisture  by  bibulous  paper  and  is  weighed  as  soon  as 
possible.  The  following  simple  formula  gives  the  propor- 
tion per  1,000  parts  of  blood: 

Weight  of  blood  used  :  Weight  of  fibrin  :  :  1,000  :  Fibrin  per  1,000. 

The  next  step  is  to  estimate  the  globules.  For  this  pur- 
pose a  portion  of  the  defibrinated  blood,  which  is  carefully 
weighed,  is  mixed  with  twice  its  volume  of  a  saturated  so- 
lution of  sulphate  of  soda  and  thrown  on  a  filter  which  has 
been  carefully  weighed,  moistened  with  distilled  water,  and 
just  before  receiving  the  mixture  of  blood  and  the  sulphate 
of  soda  is  moistened  with  the  saline  solution.  The  fluid 
which  passes  through  should  be  about  the  color  of  the 
serum;  and  if  a  few  globules  pass  at  first  the  fluid  should 
be  poured  back  until  it  is  clear.  The  funnel  is  then  covered 
and  the  fluid  allowed  to  separate,  the  blood-globules  being 
retained  on  the  filter.  The  filter  and  funnel  are  then 
plunged  several  times  in  a  vessel  of  boiling  water,  by  which 
all  the  sulphate  of  soda  which  remains  is  washed  out  and 
the  blood-globules  are  coagulated  without  changing  their 
weight.  The  funnel  should  be  covered  again  and  the  water 
allowed  to  drip  from  the  filter,  after  which  it  is  weighed, 
deducting  the  weight  of  the  moist  filter  previously  ob- 
tained, which  gives  the  weight  of  the  globules.  The  pro- 
portion of  globules  to  1,000  parts  of  blood  is  obtained 
by  the  following  formula: 

T^  Gu  ■     ^  J  ui     J        J       /-I  u  1  Defibrinated     :    Globules  per 

Uenbnnated  blood  used       Globules       :  .  1      ■  .     „„  ,  ^^^ 

blood  per  1,000  1,000. 

The  next  step  is  to  estimate  the  quantity  of  albumin 
in  the  serum  and  thence  its  proportion  in  the  blood.  For 
this  purpose  I  first  ascertain  the  quantity  of  serum  in 
1,000  parts  of  blood,  which  is  done  by  subtracting  the 
sum  of  the  fibrin  and  globules  per  i.ooo  from  1,000.  Hav- 
ing done  this  and  waited  ten  or  twelve  hours  for  specimen 
No.  2  to  separate  completely  into  clot  and  serum,  I  take 
a  small  quantity  of  the  serum,  about  half  an  ounce,  care- 
fully   weigh    it,    and   add    suddenly    twice    its    volume    of 


3o8  ORGANIC    NITROGENOUS   PRINCIPLES 

absolute  alcohol.  The  albumin  is  thus  thrown  down  in 
a  grumous  mass,  and  the  whole  is  thrown  on  a  filter  pre- 
viously moistened  with  alcohol  and  weighed.  The  funnel 
is  immediately  covered,  and  the  fluid  separates  from  the 
albumin  very  rapidly.  I  ascertain  that  no  fluid  albumin 
passes  through  the  filter  by  testing  the  fluid  with  nitric 
acid.  After  the  filter  has  ceased  to  drip,  it  is  weighed,  and 
the  weight  of  all)umin  ascertained  by  deducting  the  weight 
of  the  filter.  The  proportion  of  albumin  to  i,ooo  parts  of 
blood  is  obtained  by  the  following  formula: 

Serum  used    :   Albumin   :  :   Serum  per  i,ooo   :   Albumin  per  1,000. 

The  above  process  is  very  simple  and  easy  of  applica- 
tion; and  if  the  directions  are  carefully  followed,  it  will  give 
quite  uniform  results.  I  have  repeatedly  satisfied  myself  of 
this  fact  by  subjecting  two  specimens  of  the  same  blood  to 
the  same  process,  which  was  followed  by  almost  identical,, 
and  in  some  instances,  identical  results.  For  example,  in 
an  examination  of  human  blood,  two  equal  quantities  (34.20 
grammes)  of  defibrinated  blood  were  analyzed  for  globules;, 
one  specimen  gave  16.40  grammes  of  globules,  and  the 
other  16.43  grammes.  This  part  of  the  process  would 
seem  more  open  to  the  charge  of  inaccuracy  than  any;  yet 
the  difference  in  the  results  of  the  two  analyses  is  so  slight 
that  it  may  be  disregarded. 

In  washing  the  fibrin  I  was  at  first  led  to  use  a  saline 
solution  instead  of  pure  water;  but  as  the  mass  evidently 
gained  weight  treated  in  this  way,  I  afterward  employed 
simple  water.  Of  two  specimens  of  fibrin  from  the  same 
blood,  one,  w'hich  was  washed  with  a  solution  of  common 
salt,  spec.  grav.  loio,  gave  10.28  parts  per  1,000,  and  the 
other,  W'hich  was  washed  with  water,  gave  but  8.82  parts,  a 
diminution  of  about  14  per  cent. 

I  tried  most  of  the  methods  for  coagulating  the  albumin 
before  fixing  upon  the  one  by  absolute  alcohol.  The  object 
was  to  get  it  as  nearly  as  possible  in  its  natural  condition, 
simply  changing  its  form  from  fluid  to  semisolid,  without 
adding  anything  which  would  decompose  it  or  unite  with 
it;  and  absolute  alcohol  seemed  better  than  heat,  nitric 
acid,  the  galvanic  current  or  any  of  the  agents  by  which  it 
is  coagulated.  It  is  necessary  to  add  about  twice  the  vol- 
ume of  alcohol,  and  to  do  this  suddenly;  when  the  fluid 


ORGANIC    NITROGENOUS    PRINCIPLES  309 

Avhich  separates  by  filtration  will  be  found  to  contain  not 
a  trace  of  albumin.  Repeated  trials  of  different  specimens 
of  the  same  serum,  producing  generally  identical  results, 
led  me  to  fix  upon  this  as  the  best  method. 

It  is  easy  to  see,  after  a  few  trials,  why  this  method  of  esti- 
mation of  these  organic  matters  has  not  been  employed  by 
chemists.  The  difficulty  is  to  fix  the  standard  of  moisture; 
for  the  specimens,  even  when  on  the  balance,  lose  weight 
bv  evaporation  every  moment.  This,  of  course,  is  opposed 
to  the  ideas  of  accuracy  which  are  necessarily  ingrafted  into 
the  character  of  every  good  analytical  chemist.  One  who  is 
accustomed  to  weigh  for  hours,  perhaps,  to  avoid  a  possible 
error  of  the  thousandth  of  a  gramme,  could  hardly  consent 
to  accept  a  weight  which  is  changing  every  moment.  Com- 
plete desiccation  is  the  only  absolutely  definite  standard; 
and  in  all  these  organic  animal  analyses,  the  substance  is 
weighed  and  exposed  to  heat  over  and  over  again,  until  it 
ceases  to  lose  weight.  Although  such  accuracy  is  indis- 
pensable in  some  processes  in  physiological  chemistry, 
here  it  is  not  only  unnecessary  but  impossible.  It  is  part 
of  the  nature  of  these  substances  to  change  every  moment; 
and  when  they  are  reduced  to  such  a  condition  that  they 
will  no  longer  change,  they  have  lost  all  their  characteristics 
as  organic  principles.  What  is  most  desirable  is  an  approxi- 
mate physiological  idea  of  their  real  quantity;  and  this  is 
better  than  the  most  accurate  estimate  of  their  dry  residue. 

By  the  process  just  described,  I  have  arrived  at  the  fol- 
lowing results  in  the  few  quantitative  analyses  of  the  blood 
for  organic  principles  I  have  made.  The  variations  in  these 
constituents  in  different  states  of  the  human  system  and  in 
different  animals  are  interesting  and  important;  but  this  de- 
mands time  and  a  long  series  of  investigations.  In  the 
few  observations  here  presented,  it  has  been  my  object  to 
show  the  advantages  of  the  analytical  process  employed,  so 
that  it  can  be  applied  by  others,  and  to  give  merely  an 
analysis  of  the  healthy  human  blood;  and  the  various  ex- 
periments have  been  made  rather  to  be  able  to  fix  upon  a 
definite  process  than  with  a  view  to  comparative  results. 
Attention  has  been  directed  only  to  fibrin,  albumin  and 
globules,  for  reasons  which  have  already  been  fully  given. 
The  number  of  analyses  of  human  blood  is  not  large,  for 
it  is  not  easy  to  obtain  healthy  specimens;  and  with  the 


3IO         ORGANIC   NITROGENOUS   PRINCIPLES 

improved  notions  of  therapeutics,  it  is  difficult,  also,  to  ob- 
tain specimens  of  blood  from  patients.  The  specimens  of 
human  blood  were  taken  from  the  arm.  The  blood  of  the 
ox  was  taken  in  the  slaui^hter  house,  the  vessels  of  the  neck 
being  divided  after  the  animal  had  been  knocked  on  the 
head. 

Examination  I. — Human  Blood,  Male. — This  speci- 
men of  blood  is  assumed  to  be  perfectly  normal.  The  sub- 
ject is  twenty-seven  years  of  age,  male,  perfectly  healthy 
and  has  never  suffered  from  disease.  The  weight  is  one 
hundred  and  seventy  pounds.  The  blood  was  taken  from 
the  arm  at  i  p.  m.    The  last  meal  had  been  taken  at  8  a.  m. 

The  following  is  the  result  of  analysis  of  the  blood: 

Fibrin 8 .  82  parts  per  i  ,000. 

Albumin 329. 82      " 

Globules 495 .  59      "  " 

Examination  II.  —  Human  Blood,  Male.  —  This 
specimen  was  taken  from  a  man,  thirty-seven  years  of  age, 
calker  by  trade,  weight  two  hundred  pounds,  but  rather 
corpulent  than  muscular.  He  had  slight  constitutional 
syphilis,  and  had  been  taking  the  iodide  of  potassium,  gr.  x 
three  times  a  day,  for  about  three  weeks.  He  was  bled 
from  the  arm  about  two  hours  after  dinner. 

The  following  is  the  result  of  analysis  of  the  blood: 

Fibrin 7 .  44-  parts  per  i  ,000. 

Albumin 277. 55      "  " 

Globules 480.44      "  " 

Examination  HI. — Human  Blood,  Female. — This 
specimen  was  taken  from  a  female,  twenty-seven  years  of 
age,  weight  one  hundred  and  sixty  pounds,  dark  complex- 
ion, and  perfectly  healthy,  with  the  exception  of  a  slight 
plethoric  tendency,  as  indicated  by  occasional  epistaxis 
which  had  troubled  her  for  a  few  days.  She  menstruated 
regularly,  the  last  time  about  two  weeks  ago.  She  took 
lunch  about  11  a.  m.  and  was  bled  at  2  p.  m.  The  blood 
coagulated  rapidly,  and  in  twelve  hours  the  clot  presented 
the  "  buffed  and  cupped  "  appearance.  A  portion  of  the 
defibrinated  blood  which  was  not  used  in  the  analysis  pre- 
sented a  remarkable  example  of  gravitation  of  the  globules 
and  separation  from  the  serum.  It  stood  in  a  graduated 
glass,  and  the  upper  half,  by  actual  measurement,  con- 


ORGANIC    NITROGENOUS    PRINCIPLES  311 

sisted  of  pure  serum.*     Two  days  after  the  venesection 
the  woman  still  enjoyed  perfect  health. 

The  following  is  the  result  of  analysis  of  the  blood: 

Fibrin 16.81  parts  per  i  ,000. 

Albumin 3ii-i8 

Globules 484 .51       "  " 

Examination  IV. — Human  Blood,  Female. — This 
specimen  was  taken  from  a  woman,  twenty-eight  years  of 
age  of  somewhat  anemic  aspect.  She  had  been  taking  an 
ounce  of  sulphate  of  magnesia  every  second  day  for  two 
weeks.  The  medicine  usually  operated  three  or  four  times. 
She  was  bled  at  2  p.  m.,  having  eaten  nothing  since  8  a.  m. 

The  following  is  the  result  of  analysis  of  the  blood: 

Fibrin 1 1  ■  34  parts  per  1,000. 

Albumin 219.47      "  " 

Globules 382.95      "  " 

Examination  V. — Blood  of  the  Ox. — This  speci- 
men was  taken  from  a  small  ox,  the  throat  being  cut  after 
he  had  been  knocked  in  the  head. 

The  following  is  the  result  of  the  analysis: 

Fibrin H-  52  parts  per  1,000. 

Albumin 195 ,  24      " 

Globules 623 .  36      "  " 

Examination  VI. — Blood  of  the  Ox, — The  animal 
from  which  this. specimen  was  taken  was  rather  larger  and 
more  vigorous  than  the  one  which  furnished  the  blood  for 
Examination  V. 

The  following  is  the  result  of  the  analysis: 

Fibrin 16.27  parts  per  1,000. 

Albumin 200.85      " 

Globules 568.61 

Of  the  four  observations  on  the  human  subject,  but 
one.  Examination  I.,  can  be  taken  as  a  fair  example  of  nor- 
mal blood.  This  analysis  shows  that  the  moist  globules 
constitute  about  onv.-half  of  the  entire  mass  of  blood;  an 

*  This  tendency  of  the  globules  to  gravitate  in  defibrinated  blood  was  no- 
ticed by  Poiseuille,  and  is  mentioned  by  Bernard  who  advances  the  view  that 
one  of  the  important  functions  of  fibrin  is  to  keep  the  globules  in  uniform  sus- 
pension. (Bernard,  "  Liquides  de  I'organisme,"  tome  i.,  p.  465.)  This  is  by 
no  means  invariable.  I  have  seen  specimens  of  blood  in  which  there  was  no 
gravitation  of  the  globules  Such  a  complete  separation  as  was  presented  in 
this  specimen  of  blood  is  very  remarkable. 


312  ORGANIC   NITROGENOUS    PRINCIPLES 

estimate  which  does  not  differ  much  from  the  restdts  ob- 
tained by  others  who  have  endeavored  to  solve  this  ques- 
tion. Denis  gives  the  proportion  of  globules  in  a  person 
"  30  years  of  age,  strong  constitution,  sanguine  tempera- 
ment," 489.52  parts  per  1,000.*  Schmidt  estimates  the 
moist  globules  at  513  per  1,000  for  the  male  and  396  for 
the  female. f     Lehmann  estimates  them  at  496  i)er  i,ooo.:{; 

Albumin  constitutes  by  far  the  greatest  part  of  the  other 
organic  matters  and  equals  nearly  one-third  of  the  entire 
weight  of  blood.  As  this  is  undoubtedly  the  element  which 
nourishes  the  organic  parts  of  the  tissues,  which  form  the 
greatest  part  of  the  body,  its  pre])onderance  is  not  surpris- 
ing. The  fibrin,  even  by  this  mode  of  analysis,  is  seen  to 
exist  in  small  quantity,  sufficient,  however,  to  firmly  coagu- 
late the  whole  mass  of  blood.  One  is  surprised  in  washing 
a  large  clot  to  see  how  little  fibrin  is  necessary  to  thus  en- 
tangle all  the  globules.  The  salts  were  found  to  exist  in 
the  fibrin,  albumin  and  globules,  which  were  all  tested  for 
chlorides,  carbonates,  phosphates  and  sulphates. 

Taking  Becquerel  and  Rodier  as  authority  for  the  pro- 
portion of  fatty,  inorganic  and  extractive  matters,  the  fol- 
lowing table  represents  the  composition  of  the  blood  in  a 
healthy  adult  male  (the  author): 

COMPOSITION    OF   THE    BLOOD* 

Globules 495 .  59 

r  Water 1 5  5  •  42 

p,               I  Fibrin 8.82 

i-lasma.    •    Albumin 329.82 

1  Fats,  inorganic  salts,  and  extractives  (B.  &  R.).  10.35 

1,000.00 

Physiologists  have  not  yet  sufficient  data  to  arrive  at 
any  definite  conclusions  in  regard  to  variations  in  the 
organic  constituents  of  the  blood  as  regards  sex,  conditions 

*  Denis,  "  Memoire  sur  le  sang.,"  Paris,  1859,  p.  427. 

f  Milne  Edwards,  "  Le9ons  de  physiologie,"  etc.,  tome  i.,  p.  237. 

X  Lehmann,  "  Physiological  Chemistry,"  American  edition,  vol  i.,  p.  548. 

*  In  order  to  ascertain  whether  this  specimen  of  blood  contained  what  would 
be  considered  as  the  normal  quantity  of  organic  constituents  estimated  by  the 
old  method,  these  were  evaporated  to  dryness  and  carefully  weighed,  with  the 
following  result,  which  it  will  be  seen  corresponds  with  that  generally  obtained  : 

Fibrin 2.50  parts  per  1 ,000. 

Albumin    71-53      "  " 

Globules 125.00      "  " 

The  proportion  of  albumin  in  the  serum  was  82.07. 


ORGANIC    NITROGENOUS    PRINCIPLES  313 

of  the  system  and  in  different  animals,  which  considera- 
tions, indeed,  would  be  beyond  the  scope  of  this  paper;  but 
the  few  facts  I  have  collected  go  to  confirm  some  of  the 
■observations  which  have  already  been  made  upon  these 
points.  It  has  been  often  observed  that  the  blood  of  the  ox 
is  much  richer  in  fibrin  than  that  of  the  human  subject;  the 
former  containing-  5  to  6  parts  per  1,000  dry,  while  the  latter 
contains  but  2  or  3.  This  difference  is  shown  in  the  pre- 
ceding analyses,  where  the  blood  of  the  ox  is  found  to  con- 
tain 14.52  to  16.27  parts  of  moist  fibrin,  human  blood  con- 
taining but  8.82  parts.  The  analyses  also  show  a  greater 
quantity  of  fibrin  in  the  two  specimens  of  blood  of  the  fe- 
male than  in  the  blood  of  the  male.  In  the  observations  of 
■others,  the  quantity  has  not  been  found  to  vary  much  in 
the  sexes.  In  this  instance,  neither  of  the  specimens  from 
the  female  can  be  taken  as  perfectly  normal ;  as  in  Examina- 
tion III.  the  subject  was  plethoric,  and  in  Examination  IV. 
she  had  been  taking  sulphate  of  magnesia  and  was  some- 
what anemic. 

The  albumin  was  found  to  vary  considerably  in  the 
specimens  of  human  blood,  being  more  abundant  in  the 
blood  of  the  male  in  Examination  I.  than  in  the  female 
in  Examinations  III.  and  IV..  but  less  in  the  blood  of  the 
male  in  Examination  II.  than  in  the  female  in  Examina- 
tion III.  There  are  not  here  sufficient  data  to  lead  to 
any  conclusion  in  regard  to  the  variations  of  albumin  in 
the  sexes.  In  the  blood  of  the  ox  the  albumin  was  much 
less  than  in  human  blood. 

The  quantity  of  globules  was  found  to  be  greater  in  the 
male  than  in  the  female.  This  has  been  noticed  by  all  ob- 
servers who  have  directed  their  attention  to  this  point,  and 
is,  perhaps,  one  of  the  most  characteristic  of  the  differences 
between  the  blood  of  the  male  and  of  the  female.  One  of 
the  females  was  slightly  plethoric,  which  caused  the  glob- 
ules to  mount  up  nearly  to  the  standard  in  the  healthy 
male.  This  condition  of  plethora,  according  to  Andral, 
is  dependent  almost  entirely  upon  an  increase  in  the  glob- 
ules. The  difference  in  this  respect  between  the  blood  of 
the  female  who  was  slightly  plethoric,  and  the  other,  who 
was  somewhat  anemic,  is  very  marked;  in  the  former  the 
globules  are  484.51  and  in  the  latter,  382.95.  The  blood  of 
the  ox  was  found  to  be  very  rich  in  globules. 


314  ORGANIC   NITROGENOUS   PRINCIPLES 

In  conclusion,  I  may  say  that  I  have  not  attempted  to 
settle  the  normal  constitution  of  the  blood,  much  less  to 
follow  out  the  variations  to  which  it  is  subject.  This  would 
require  a  largely  extended  series  of  observations.  But, 
considering  a  proper  idea  of  the  condition  of  existence  of 
the  organic  ingredients  of  great  importance  to  the  physiolo- 
gist and  physician,  I  have  endeavored  to  study  this  fluid 
from  a  physiological  point  of  view;  and  with  the  ideas  I 
have  been  led  to  entertain  on  this  subject,  it  seemed  that  a 
new  method  of  analysis  which  would  give  real  propor- 
tions of  these  principles  was  indispensable.  My  object  has 
been  merely  to  settle  upon  some  rational  and  simple  proc- 
ess, leaving  its  extended  applications  to  be  made  in  the 
future.  The  process  I  have  described  seems  to  me  suffi- 
ciently accurate  for  all  practical  purposes;  and  it  is  so 
easy  of  application  that  I  can  not  but  indulge  the  hope 
that  others  may  be  led  to  cultivate  this  interesting  and 
fruitful  field  of  inquiry. 


XIV 

EXPERIMENTS  UNDERTAKEN  FOR  THE  PUR- 
POSE OF  RECONCILING  SOME  OF  THE  DIS- 
CORDANT OBSERVATIONS  ON  THE  GLYCO- 
GENIC FUNCTION  OF  THE  LIVER 

Published  in  the  "  New  York  Medical  Journal  "  for  November,  1869. 

When  it  was  announced  by  Bernard,  in  1848,  that  he 
had  discovered  a  new  and  important  function  of  the  Hver, 
there  being  in  this  organ  a  constant  production  of  the 
same  variety  of  sugar  that  had  long  been  recognized  in 
the  urine  of  diabetic  patients,  the  great  physiological  and 
pathological  importance  of  the  discovery,  attested,  as  it 
was,  by  experiments  which  seemed  to  be  absolutely  con- 
clusive in  their  results,  excited  the  most  profound  scientific 
interest.  During  the  present  century,  indeed,  there  have 
been  few  physiological  questions  which  have  attracted  so 
much  attention;  and  the  observations  of  Bernard  were 
soon  repeated,  modified  and  extended  by  experimentalists 
in  different  parts  of  the  world.  In  1857  Bernard  discov- 
ered a  sugar-forming  material  in  the  liver,  analogous  in 
its  composition  and  properties  to  starch;  and  this  seemed 
to  complete  the  history  of  glycogenesis. 

I  do  not  propose  at  this  time  to  give  an  extended  re- 
view of  the  experiments  which  have  been  made  in  different 
parts  of  the  world  with  the  view  either  of  confirming  or 
overthrowing  the  theory  advanced  by  Bernard,  but  shall 
discuss  the  two  opinions  wdiich  are  now  most  prevalent  in 
English  and  French  physiological  literature.  These  two 
opinions  are  the  following: 

Those  who  accept  the  experiments  of  Bernard  as  con- 
clusive assume  that  the  substance  of  the  liver  and  the  blood 
in  the  hepatic  veins  always  contain  sugar.  This  sugar  is 
believed  to  be  formed  in  the  so-called  hepatic  cells,  from 

315 


3i6      GLYCOGENIC    FUNCTION    OF    THE    LIVER 

the  glycogen  contained  in  them,  and  to  be  taken  up  by 
the  blood  as  it  passes  through  the  liver,  existing  in  the 
hepatic  veins,  the  ascending  vena  cava  and  the  right  side 
of  the  heart.  It  usually  disappears  from  the  blood  in  its 
passage  through  the  lungs.  Sugar  is  believed  always  to 
exist  in  the  liver,  the  blood  of  the  hepatic  veins  and  of  the 
right  side  of  the  heart,  independently  of  the  kind  of  food 
used.  In  the  carnivora  the  blood  of  the  portal  system 
never  contains  sugar  when  the  animal  is  confined  to  a  diet 
of  nitrogenous  and  fatty  matters;  but  sugar  is  found  none 
the  less  invariably  in  the  liver  and  in  the  vascular  system 
between  this  organ  and  the  heart. 

Others  have  accepted  the  view  advanced  by  Dr.  Pavy, 
of  Guy's  Hospital,  w'ho  professes  to  have  demonstrated 
that  neither  the  liver  nor  the  blood  circulating  between  the 
liver  and  the  heart  ever  contains  sugar  during  life;  but 
that  the  sugar  which  has  been  found  in  these  situations 
is  the  result  of  a  post-mortem  change  of  the  glycogenic 
matter,  or  as  it  is  called  by  Dr.  Pavy,  the  amyloid  matter 
of  the  liver. 

These  two  opposite  views  are  supported  by  experiments 
which  seem  to  be  conclusive;  yet  it  is  evident  that,  if  the 
observations  in  both  instances  are  entirely  accurate,  they 
must  prove  precisely  the  same  fact.  It  was  in  the  hope  of 
harmonizing  these  discordant  opinions,  that  I  undertook 
some  modifications  of  the  experiments  of  Bernard  and 
Pavy.  I  shall  not  discuss  the  accuracy  of  the  methods 
employed  by  these  observers  but  intend  merely  to  follow 
out  a  train  of  reasoning,  which  seems  to  me  to  be  fully 
sustained  by  experiment  and  which  I  believe  will  lead  to 
a  correct  interpretation  of  the  apparently  opposite  results 
heretofore  obtained. 

Since  the  summer  of  1858  I  have  been  in  the  habit 
of  repeating,  several  times  each  year,  the  experiments  by 
which  Bernard  demonstrated  the  glycogenic  function  of 
the  liver,  performing  the  experiments  chiefly  as  class- 
demonstrations.  I  have  followed  most  of  the  modifica- 
tions of  these  experiments  which  have  been  published  by 
Bernard  from  time  to  time  and  I  have  almost  always  con- 
firmed his  results  in  every  particular.  I  have  never  failed 
to  demonstrate  the  absence  of  sugar  in  the  blood  of  the 
portal  system,  when  the  specimens  were  taken  with  proper 


GLYCOGENIC    FUNCTION    OF    THE    LIVER      317 

precautions  from  carnivorous  animals  that  had  taken 
neither  starch  nor  sugar  into  the  ahmentary  canal.  I  have 
found  it  important  to  apply  a  hgature  rapidly  to  the  portal 
vein  as  it  penetrates  the  liver  and  to  make  a  very  small 
opening  into  the  abdominal  cavity  in  this  step  of  the  ex- 
periment. When  I  have  detected  a  trace  of  sugar  in  the 
clear  extract  from  the  portal  blood  of  an  animal  in  the 
condition  just  mentioned,  it  has  been  consequent  upon 
delay  in  seizing  the  vein;  and  I  have  anticipated  the  prob- 
ability of  finding  sugar  from  blood,  which,  under  these 
circumstances,  regurgitates  from  the  liver.  The  necessity 
of  employing  these  precautions  is  fully  insisted  upon  by 
Bernard.  I  have  never  failed  to  find  sugar  in  the  blood 
of  the  hepatic  veins  of  healthy  dogs  that  had  taken  neither 
starch  nor  sugar  into  the  alimentary  canal.  In  my  earlier 
experiments  I  never  failed  to  find  a  great  abundance  of 
sugar  in  the  substance  of  the  liver,  in  dogs  under  the 
same  conditions.  In  one  instance,  however,  in  the  winter 
of  i859-'6o,  I  failed  to  find  sugar  in  the  liver  of  a  dog  that 
was  affected  with  what  is  known  as  "mange";  but  I 
considered  this  to  be  due  to  the  peculiar  condition  of 
the  animal. 

On  several  occasions  I  have  repeated  Bernard's  experi- 
ment of  analyzing  for  sugar,  the  portal  blood,  the  sub- 
stance of  the  liver,  the  hepatic  blood,  the  blood  from  the 
right  side  of  the  heart,  the  substance  of  the  lungs,  the  blood 
from  the  arterial  system,  and  the  substance  of  the  muscles, 
the  kidneys  and  the  spleen,  all  the  specimens  being  taken 
from  the  same  animal.  I  have  always  found  that  sugar 
existed  only  in  the  substance  of  the  liver,  the  blood  from 
the  hepatic  veins,  and  the  right  side  of  the  heart  and  in  no 
other  situations;  showing,  apparently,  that  sugar  is  con- 
stantly being  produced  by  the  liver  and  is  carried  by  the 
circulating  blood  to  the  lungs,  there  to  be  destroyed. 
On  several  occasions  I  have  drawn  the  blood  from  the 
right  side  of  the  heart  of  a  living  animal,  by  catheteriza- 
tion through  an  opening  into  the  right  external  jugular 
vein  (a  manipulation  which  presents  no  difficulty),  and 
have  never  failed  to  find  sugar.  This  experiment  I  have 
done  without  the  administration  of  ether,  following  the 
operative  procedure  described  by  Bernard. 

I  have  also  frequently  repeated  the  experiment  of  pgss- 


3i8      GLYCOGENIC    FUNCTION    OF    THE    LIVER 

ing  a  stream  of  water  through  the  Hver  from  the  portal 
vein,  by  which  all  the  sugar  can  be  removed  in  a  short 
time,  and  testing  the  sulistance  of  the  Hver  a  few  hours 
after,  it  having  been  kept  in  the  mean  time  at  a  tempera- 
ture of  80°  to  100°  Fahr.  In  this  experiment  I  have  al- 
ways found  an  abundance  of  sugar.  The  glycogen  out 
of  which  this  secondary  formation  of  sugar  is  supposed  to 
take  place,  I  have  extracted  and  studied  after  the  method 
proposed  by  Bernard  and  have  confirmed  his  observations 
on  this  substance  in  every  particular. 

In  these  experiments  I  have  used  the  various  copper 
tests;  viz.,  Trommer's,  Barreswill's  and  Fehling's,  and  have 
made  my  clear  extracts,  generally  by  boiling  with  an  ex- 
cess of  sulphate  of  soda,  but  very  often  by  mixing  the 
blood  or  the  watery  extracts  of  the  tissues  with  animal 
charcoal  and  filtering. 

The  theory  advanced  by  Pavy,  that  sugar  is  not  pro- 
duced by  the  liver  during  life  and  that  when  this  substance 
is  found  in  the  liver  it  is  the  result  of  post-mortem  change 
of  the  glycogen  (which  he  calls  the  amyloid  substance), 
always  seemed  to  me  to  be  invalidated  by  the  experiment 
of  catheterization  of  the  right  side  of  the  heart  in  a  living 
animal  without  the  administration  of  ether;  for  in  the  blood 
taken  under  these  conditions,  the  presence  of  sugar  is  un- 
mistakable. The  admission  that  sugar  is  contained  in 
the  blood  passing  out  of  the  liver,  when  ether  has  been 
administered,  and  the  fact  that  sugar  is  sometimes  pro- 
duced in  the  body,:  in  cases  of  diabetes  mellitus  (for  there 
are  undoubted  cases  in  which  sugar  is  discharged  in  the 
urine,  when  neither  starch  nor  sugar  has  been  taken  as 
food),  point  to  the  probable  normal  production  and  de- 
struction of  this  substance  in  the  economy.  Sugar  can 
hardly  be  regarded  as  a  heterologous  substance  or  as  a 
product  of  decomposition;  and  it  constitutes  an  important 
article  of  food,  from  the  fact  that  it  is  consumed  in  the 
body  in  connection  with  certain  of  the  processes  of  nutri- 
tion. 

Dr.  Pavy  asserts  that  the  liver  never  contains  sugar 
during  life;  but  that  after  death,  it  is  formed  out  of  the 
amyloid  substance,  and  its  proportion  goes  on  increas- 
ing for  a  number  of  hours,  particularly  when  the  organ 
is  kept  at  about  the  temperature  of  the  body.     The  ex- 


GLYCOGENIC    FUNCTION    OF   THE    LIVER      319 

periments  of  Bernard  with  a  liver  washed  out  with  a 
stream  of  water  also  show  that  sugar  may  be  produced 
after  death. 

I  was  led  to  perform  the  following  experiments  by  the 
fact  that  of  late  years,  the  experiments  by  which  I  have 
been  in  the  habit  of  demonstrating  the  glycogenic  func- 
tion of  the  liver  have  inclined  me  to  the  opinion  that  the 
observations  detailed  by  Dr.  Pavy  are  entirely  accurate; 
and  that  the  error  consists  in  his  interpretation  of  the 
facts.  The  circumstances  which  led  to  this  view  were  the 
following: 

I  formerly  was  in  the  habit  of  making  my  demonstra- 
tions of  the  formation  of  sugar  in  the  liver  upon  animals 
that  had  been  etherized;  and  then  I  always  obtained  a 
brilliant  precipitate  from  a  clear  extract  of  the  substance 
of  the  liver,  boiled  with  the  test-liquid.  I  performed  the 
experiment  in  this  way  before  I  had  acquired  sufficient  dex- 
terity to  seize  the  portal  vein  readily  and  to  go  through 
with  the  necessary  manipulations  with  rapidity.  I  subse- 
quently made  the  operation  by  first  suddenly  breaking  up 
the  medulla  oblongata,  then  making  a  small  incision  into 
the  abdominal  cavity  and  seizing  the  portal  vein  instantly, 
following  out  the  remaining  steps  of  the  experiment  with- 
out delay.  In  this  way,  although  I  always  found  sugar 
in  the  blood  of  the  hepatic  veins,  I  frequently  failed  to 
obtain  a  distinct  reaction  in  the  extract  of  the  liver;  and 
the  more  accurately  and  rapidly  the  operation  was  per- 
formed, the  more  difficult  was  it  to  detect  sugar  in  the 
hepatic  substance. 

It  occurred  to  me,  in  reflecting  upon  these  facts,  that 
inasmuch  as  no  one  has  assumed  that  the  actual  quantity 
of  sugar  produced  by  the  liver  is  very  considerable,  and 
as  a  large  quantity  of  blood  (in  which  the  sugar  is  very 
soluble)  is  constantly  passing  through  the  organ,  precise- 
ly as  water  is  passed  through  its  vessels  to  wash  out  the 
sugar,  the  sugar  might  be  washed  out  by  the  blood  as 
fast  as  it  is  formed;  and  really  the  liver  might  never  con- 
tain sugar  in  its  substance,  as  a  physiological  condition, 
although  it  is  constantly  engaged  in  its  production.  It 
is  well  known  that  the  characteristic  elements  of  the  vari- 
ous secretions  proper  are  produced  in  the  substance  of  the 
glands  and  are  washed  out  at  the  proper  time  by  liquid 


320      GLYCOGENIC    FUNCTION    OF   THE    LIVER 

derived  from  the  blood,  which  circulates  in  the  g^lands  dur- 
ing their  functional  activity  in  very  much  greater  quantity 
than  during  the  intervals  of  secretion.  The  liver-sugar  may 
be  regarded  as  an  element  of  secretion;  and  possibly  it 
may  be  completely  washed  out  of  the  liver,  as  fast  as  it 
is  formed,  by  the  current  of  blood,  the  hepatic  vein,  in  this 
regard,  serving  as  an  excretory  duct. 

To  put  this  hypothesis  to  the  test  of  experiment,  it 
was  necessary  to  obtain  and  analyze  the  liver  in  a  con- 
dition as  near  as  possible  to  that  under  which  it  exists  in 
the  living  organism;  and  in  carrying  out  this  idea,  I  made 
the  following  experiments: 

Experiment  I. — A  medium-sized  dog,  full  grown,  in  good  con- 
dition and  not  in  digestion  was  held  upon  the  operating-table  by 
two  assistants  and  the  abdomen  was  widely  opened  by  a  single 
sweep  of  the  knife.  A  portion  of  the  liver,  weighing  about  two 
ounces,  was  then  cut  off  and  immediately  cut  into  small  pieces, 
which  were  allowed  to  fall  into  boiling  water.  The  time  from  the 
first  incision  until  the  liver  was  in  the  boiling  water  was  twenty- 
eight  seconds.  An  excess  of  crystalHzed  sulphate  of  soda  was 
then  added,  and  the  mixture  was  boiled  for  about  five  minutes.  It 
was  then  thrown  upon  a  filter  and  the  clear  fluid  which  passed 
through  was  tested  for  sugar  by  Trommer's  test.  The  reaction 
was  doubtful  and  presented  no  marked  evidence  of  sugar. 

Experiment  II. — A  medium-sized  dog,  in  the  same  condition 
as  the  animal  in  the  first  experiment,  was  held  upon  the  table  and 
a  portion  of  the  liver  excised  as  above  described.  The  whole  oper- 
ation occupied  twenty-two  seconds.  But  ten  seconds  elapsed  from 
the  time  the  portion  of  the  liver  was  cut  off  until  it  was  in  the 
boiling  water.  It  was  boiled  for  about  fifteen  minutes,  made  into 
a  paste  with  animal  charcoal  and  thrown  upon  a  filter.  The  clear 
fluid  which  passed  through  was  tested  for  sugar  by  Trommer's 
test.     There  was  no  marked  evidence  of  sugar. 

Experiment  III. — A  large  dog,  full  grown  and  fed  regularly 
every  day,  but  not  in  digestion  at  the  time  of  the  experiment,  was 
held  firmly  upon  the  table.  This  dog  had  been  in  the  laboratory 
about  a  week  and  was  in  a  perfectly  normal  condition.  The  ab- 
dominal cavity  was  opened  and  a  piece  of  the  liver  was  cut  off  and 
thrown  into  boiling  water,  the  time  occupied  in  the  process  being 
ten  seconds.  Before  the  liver  was  cut  up  into  the  boiling  water, 
the  blood  was  rinsed  off  in  cold  water.  The  liver  was  boiled  for 
about  seventeen  minutes,  mixed  with  animal  charcoal  and  the 
whole  thrown  upon  a  filter. 

Immediately  after  cutting  off  a  portion  of  the  liver  and  throw- 
ing it  into  boiling  water,  the  medulla  oblongata  was  broken  up; 
a  ligature  was  applied  to  the  ascending  vena  cava  just  above  the 
renal  veins ;  the  chest  was  opened,  and  a  ligature  was  applied  ta 
the  vena  cava  just  above  the  opening  of  the  hepatic  veins.     A 


GLYCOGENIC    FUNCTION    OF    THE    LIVER      321 

specimen  of  blood  was  then  taken  from  the  hepatic  veins.  This 
part  of  the  operation  occupied  not  more  than  one  minute.  A 
little  water  was  added  to  the  blood,  which  was  boiled  briskly,  mixed 
with  animal  charcoal  and  thrown  upon  a  filter.  The  liquids  which 
passed  through  from  both  specimens  were  perfectly  clear. 

While  the  filtration  was  going  on,  Fehling's  test  liquid  (a  mix- 
ture of  sulphate  of  copper,  neutral  tartrate  of  potash  and  caustic 
soda)  was  made  up,  so  as  to  be  perfectly  fresh. 

The  two  liquids  were  then  carefully  tested  for  sugar  with  this 
solution.  The  extract  of  the  liver  presented  not  the  slightest  trace 
of  sugar.  The  extract  from  the  blood  of  the  hepatic  veins  pre- 
sented a  well-marked  deposit  of  the  oxide  of  copper,  revealing 
unequivocally  the  presence  of  a  small  quantity  of  sugar. 

In  these  experiments  I  did  not  attempt  to  show  the 
absence  of  sngar  in  the  l)lood  of  the  portal  system;  for  it 
would  have  been  difficult,  if  not  impossible,  to  have  de- 
monstrated this  and  at  the  same  time  to  have  obtained 
the  specimens  of  liver  as  rapidly  as  I  desired.  The  fact 
that  the  portal  blood  in  a  carnivorous  animal  that  has 
taken  no  saccharine  or  starchy  matters  into  the  alimen- 
tary canal  contains  no  sugar.  I  regarded  as  settled  by  the 
experiments  of  Bernard,  which  I  have  repeatedly  con- 
firmed. Neither  did  I  attempt  to  show^  that  sugar  exists 
in  the  liver  when  a  certain  period  has  elapsed  after  death; 
for  this  fact  has  been  demonstrated  by  all  who  have  ex- 
perimented on  the  subject.  I  desired  only  to  ascertain 
whether  the  liver  taken  from  a  living  animal,  and  the 
change  of  the  glycogen  arrested  before  any  sugar  has  had 
time  to  make  its  appearance,  if  its  formation  is  post  mor- 
tem, really  contained  sugar.  A  few  seconds  only  elapsed 
before  the  liver  was  cut  up  into  boiling  water  (which  will 
effectually  arrest  the  transformation  of  the  glycogenic 
matter),  and  the  presence  of  sugar  in  the  decolorized  ex- 
tract could  not  be  demonstrated.  In  Experiment  III.  par- 
ticularly, very  delicate  tests  were  employed  with  the  great- 
est care;  and  although  the  extract  of  the  liver  contained 
no  sugar,  the  presence  of  sugar  in  the  blood  coming  from 
the  liver  w^as  unmistakable.  This  experiment  was  pecul- 
iarly successful;  and  I  could  hardly  expect  to  be  able  to 
collect  the  specimens  with  less  delay.  Anesthetics  were 
not  employed  in  any  of  the  experiments,  and  there  seemed 
to  be  no  circimistance  that  could  interfere  with  the  normal 
character  of  the  specimens  examined.  The  animals  were 
perfectly   quiet   when   the   experiments  were   begun,   and 


322      GLYCOGENIC   FUNCTION   OF   THE    LIVER 

they  were  operated  upon  as  soon  as  they  were  put  upon 
the  table,  the  respiration  and  circulation  being  apparently 
normal. 

CONCLUSIONS 

Although  these  experiments  are  not  entirely  new,  my 
interpretation  of  them  serves  to  harmonize,  in  my  owai 
mind  at  least,  the  results  obtained  by  Bernard  and  by 
Pavy : 

L  A  substance  exists  in  the  healthy  liver,  which  is 
capable  of  being  converted  into  sugar;  and  inasmuch  as 
this  is  changed  into  sugar  during  life,  the  sugar  being 
washed  away  by  the  blood  passing  through  the  liver,  it 
is  proper  to  call  it  glycogen,  or  sugar-forming  matter. 

IL  The  liver  has  a  glycogenic  function,  which  consists 
in  the  constant  formation  of  sugar  out  of  the  glycogen, 
this  sugar  being  carried  away  by  the  blood  of  the  hepatic 
veins,  which  always  contains  a  certain  proportion  of  sugar, 
and  subserving  some  purpose  in  the  economy  connected 
with  nutrition,  as  yet  imperfectly  understood.  This  pro- 
duction of  sugar  takes  place  in  the  carnivora  as  well  as 
in  those  animals  that  take  sugar  and  starch  as  food;  and 
it  is  essentially  independent  of  the  kind  of  food  taken. 

in.  During  life  the  liver  contains  only  the  glycogen 
and  no  sugar,  because  the  great  mass  of  blood  which  is 
constantly  passing  through  this  organ  washes  out  the  su- 
gar as  fast  as  it  is  formed;  but  after  death  or  when  the  cir- 
culation is  interfered  with,  the  transformation  of  glycogen 
into  sugar  goes  on;  the  sugar  is  not  removed  under  these 
conditions,  and  can  then  be  detected  in  the  substance  of 
the  liver. 


XV 

THE  TREATMENT   OF   DIABETES   MELLITUS  * 

Published  in  the  "Journal  of  the  American  Medical  Association" 
for  July  12,  1884. 

It  would  not  be  possible,  within  the  Hmits  to  which  this 
paper  is  necessarily  restricted,  to  discuss  satisfactorily  the 
pathology  or  even  the  clinical  history  of  diabetes  mellitus, 
although  the  disease  in  question  is  one  of  the  most  interest- 
ing as  well  as  obscure  affections  which  the  physician  is 
called  upon  to  treat.  While  the  study  of  diabetes  and  of  its 
attendant  disorders  of  general  nutrition  presents  difficulties, 
as  regards  questions  of  causation  and  pathology,  that  seem 
almost  insurmountable,  when  attention  is  once  directed  to 
the  simple  problem  of  the  presence  of  sugar  in  the  urine, 
this  condition  is  now  easily  and  certainly  recognizable.  It 
is  probably  true  that  sugar  exists  in  the  urine  of  a  certain 
number  of  persons,  unattended  with  symptoms,  so  that  it  is 
detected  only  by  accident  or  may  never  be  revealed,  such 
persons  having  no  apparent  occasion  to  seek  medical  ad- 
vice. In  an  experience  in  life  insurance  examinations  ex- 
tending through  a  period  of  nearly  thirteen  years,  I  have 
found  a  small  quantity  of  sugar  in  the  urine  of  applicants 
who  supposed  themselves  to  be  perfectly  healthy;  but  with- 
in the  time  mentioned,  only  five  such  cases  have  come 
under  my  observation.  Three  of  these  applicants  are  now 
living  and  are  presumably  in  good  health,  the  sugar  in  the 
urine  having  been  noted  eight  to  twelve  years  ago;  one 
case  was  lost  sight  of  and  one  applicant  is  reported  to 
have  died  of  hemoptysis  nine  months  after  the  examina- 
tion of  the  urine.  During  the  time  mentioned;  viz..  twelve 
years  and  nine  months.  I  examined  1,884  persons  who  sup- 
posed themselves  to  be  in  good  health  and  nearly  always 

*  Read  in  the  Section  on  Practice  of  Medicine  and  Materia  Medica  of  the 
American  Medical  Association,  in  May,  1884. 

323 


324         TREATMENT    OF    DIABETES    MELLITUS 

made  examinations  of  the  urine.  All  of  the  applicants,  with 
one  or  two  exceptions,  were  males.  The  proportion,  there- 
fore, of  apparently  healthy  persons  in  whose  urine  I  have 
found  sugar  is  very  small  (i  in  377);  but  even  this  shows 
that  sugar  may  be  present  in  the  urine,  either  as  a  transient 
or  an  insignificant  condition  or  existing  without  any  of  the 
general  symptoms  of  diabetes. 

In  the  great  proportion  of  cases  of  diabetes  that  come 
under  observation,  attention  has  been  directed  to  the  con- 
dition of  the  urine  by  certain  general  symptoms,  such  as 
excessive  thirst,  persistent  polyuria,  a  sensation  of  dryness 
of  the  mouth  and  fauces,  fatigue  after  moderate  muscular 
exertion  or  some  slight  affection  of  the  external  genitals. 
In  a  case  of  diabetes  that  I  have  had  under  treatment  for 
nearly  four  years,  now  under  observation,  the  patient  first 
consulted  a  physician  for  herpes  progenitalis,  which  led  to 
an  examination  of  the  urine.  In  females,  persistent  pruritus 
of  the  vulva  is  often  the  first  trouble  pointing  to  the  possi- 
ble existence  of  diabetes.  In  several  cases  I  have  detected 
sugar  in  the  urine  when  pruritus  vulvae  was  the  only  trouble 
complained  of  by  patients.  So  constant  is  this  symptom^ 
that  diabetes  should  always  be  suspected  when  the  pruritus 
persists  without  any  apparent  cause  and  resists  ordinary 
measures  of  treatment.  The  pruritus  is  seldom  absent  when 
the  proportion  of  sugar  in  the  urine  is  considerable. 

Detection  of  Sugar  in  the  Urine. — So  far  as  purely 
clinical  examination  of  the  urine  is  concerned,  the  great 
desideratum  is  a  simple  test,  easy  and  rapid  in  its  appli- 
cation, upon  which  one  can  rely  with  absolute  confidence. 
I  shall  pass  over,  without  discussion  or  even  mention,  the 
different  tests  employed  for  the  detection  of  sugar,  except 
the  one  known  as  Fehling's.  When  the  Fehling's  liquid  is 
properly  prepared  and  carefully  used,  there  can  be  no  error 
in  the  results.  If  a  quantity  of  this  test,  however,  be  made 
and  kept  for  some  time,  it  is  liable  to  change  so  as  to  be- 
come more  or  less  unreliable.  This  want  of  stability  in  the 
test-liquid  has  long  been  recognized  by  those  accustomed 
to  urinary  examinations;  and  a  few  years  ago  I  prepared 
three  separate  liquids,  which  I  mixed  in  certain  proportions 
for  use  as  required.  Even  this  did  not  prove  to  be  entirely 
satisfactory.  Within  the  last  year,  two  separate  liquids  have 
been  prepared  by  Dr.  E.  R.  Squibb,  and  are  kept  by  him 


TREATMENT    OF    DIABETES    MELLITUS         325 

for  sale,  in  which  form  the  test  seems  to  leave  nothing  to 
be  desired  in  the  qualities  of  accuracy  and  ease  of  applica- 
tion. The  test,  as  it  is  now  prepared  by  Dr.  Squibb,  is 
simply  perfect;  but  so  much  depends  upon  its  proper  use, 
that  I  venture  to  give  an  account  of  its  application  and  the 
necessary  precautions  to  be  adopted.  These  precautions 
are  simple  and  demand  no  special  skill;  but  they  often  be- 
come very  important,  especially  in  determining  with  cer- 
tainty the  absence  of  sugar. 

The  two  test-liquids  are  prepared  by  Dr.  Squibb  accord- 
ing to  the  following  formulas: 

For  the  Solution  of  Cupric  Sulphate. — Use  puri- 
fied sulphate  of  copper,  in  granular  crystals,  air-dried. 
Weigh  2^^  grains  (17.32  grammes)  of  the  salt  and  dissolve 
it  in  about  4  fluidounces  (120  cc.)  of  distilled  water,  adding 
about  4  minims  {\  cc.)  of  pure  sulphuric  acid.  /\dd  dis- 
tilled water  to  this  solution  to  make  8^  fluidounces  (260 
cc). 

For  the  Solution  of  Alkaline  Tartrates. — Weigh 
2  ounces,  391  grains  (87.5  grammes)  of  re-crystallized 
sodio-potassic  tartrate,  or  Rochelle  salt,  and  dissolve  it  in 
about  6  fluidounces  (175  cc.)  of  distilled  water.  Filter  the 
solution,  if  necessary,  and  add  it  to  a  clear  solution  of  386 
grains  (25  grammes)  of  caustic  soda  in  about  if  fluidounces 
(50  cc.)  of  distilled  water.  Add  distilled  water  to  this 
solution  to  make  %\  fluidounces  (260  cc). 

These  two  solutions  are  to  be  kept  in  separate  bottles 
for  use.  If  they  are  made  with  accuracy  and  mixed  together 
in  equal  proportions,  two  hundred  grains  of  the  mixture 
will  be  decolorized  by  exactly  one  grain  of  sugar,  or  each 
cubic  centimetre  of  the  mixture  will  be  decolorized  by  0.005 
of  a  gramme  of  sugar.  The  liquids  can  therefore  be  em- 
ployed for  quantitative  estimates,  although  I  shall  describe 
the  use  of  the  test  simply  for  determining  the  fact  of  the 
presence  or  absence  of  sugar. 

For  use  in  qualitative  analysis,  the  two  liquids  may  be 
roughly  mixed  in  about  equal  proportions  in  a  test-tube  or 
they  may  be  measured  accurately  and  diluted  with  about  an 
equal  volume  of  distilled  water.  The  latter  process  should 
be  resorted  to  in  all  delicate  analyses. 

For  ordinary  use  the  following  process  may  be  em- 
ployed: 


326        TREATMENT    OF    DIABETES    MELLITUS 

Mix  in  a  test-tube  equal  volumes  of  the  two  li(|uids  so 
that  the  mixture  will  extend  in  the  tul)e  to  the  length  of 
about  an  inch. 

Bring  the  mixture  to  the  boiling  point  and  then  add  to 
the  boiling  test  a  quantity  of  urine  e([ual  to  that  of  the  test. 

Bring  the  mixture  of  the  test-liquid  and  urine  to  the 
boiling  point  and  then  allow  it  to  cool. 

If  no  distinct  and  opaque  reddish  or  yellowish  precipi- 
tate is  present  when  the  mixture  of  test  and  urine  has  be- 
come cool  after  the  second  boiling,  it  is  certain  that  no  sugar 
is  present. 

All  these  precautions  are  essential;  and  I  have  repeat- 
edly examined  specimens  of  urine  in  which  the  character- 
istic precipitate  due  to  the  presence  of  sugar  did  not  occur 
until  one  or  two  minutes  had  elapsed  after  the  second  boil- 
ing. 

In  very  delicate  testing,  take  a  definite  quantity  of  the 
copper  solution,  add  an  equal  quantity  of  distilled  water, 
add  then  of  the  solution  of  alkaline  tartrates  a  quantity  equal 
to  the  cjuantity  of  the  copper  solution,  and  add  finally  dis- 
tilled water  in  the  same  quantity.  When  this  mixture  is 
boiled,  if  the  test  is  not  absolutely  perfect,  there  will  be  a 
precipitate  before  the  urine  is  added.  The  mixture,  if 
perfect,  may  be  used  in  the  same  way  as  the  simple  un- 
diluted mixture  of  the  two  solutions. 

When  sugar  is  present  in  the  urine,  an  opaque  yellow- 
ish or  reddish  precipitate  appears  at  some  time  during  the 
process,  the  promptness  of  its  appearance  and  its  quantity 
being  in  direct  proportion  to  the  quantity  of  sugar. 

It  is  often  important  to  be  able  to  determine,  at  least 
approximately,  the  quantity  of  sugar  discharged  in  twenty- 
four  hours  or  its  proportion  per  fluidounce.  Using  the 
volumetric  process,  this  estimate  requires  some  practice 
and  occupies  twenty  to  thirty  minutes;  but  the  "differ- 
ential density  method  "  recommended  by  Roberts,  is  very 
simple  and  is  sufficiently  accurate  for  ordinary  purposes. 
With  a  little  practice,  indeed,  it  may  be  employed  by  in- 
telligent patients. 

Two  specimens  of  diabetic  urine  are  taken,  about  four 
ounces  of  each,  one  for  comparison  and  the  other  for  anal- 
ysis. To  one  is  added  a  lump  of  German  yeast,  about  the 
size  of  a  filbert,  in  a  bottle  with  a  cork  nicked  to  allow^  the 


TREATMENT    OF    DIABETES    MELLITUS         327 

escape  of  gas;  and  the  other  specimen  is  placed  in  a  similar 
bottle  tightly  corked.  The  bottles  are  then  put  aside  in  a 
warm  place,  as  the  mantelpiece  in  winter  or  in  the  sun  in 
summer.  In  the  course  of  twenty-four  hours,  fermentation 
will  have  been  completed  in  the  specimen  to  which  yeast  has 
been  added.  If  the  specific  gravity  of  the  two  specimens 
is  then  compared,  the  fermented  specimen  will  be  found 
much  the  lighter,  from  loss  of  the  sugar  which  has  been 
decomposed  into  alcohol  and  carbonic  acid.  The  differ- 
ence in  the  density  of  the  two  specimens,  expressed  in  de- 
grees of  the  urinometer,  will  represent  the  number  of  grains 
of  sugar  per  fluidounce  in  the  urine.  For  example,  if  the 
specific  gravity  of  the  fermented  specimen  is  loio,  and  the 
specific  gravity  of  the  unfermented  specimen,  1040,  the 
urine  contains  thirty  grains  of  sugar  per  fluidounce.  In 
this  process  it  is  essential  to  compare  the  density  of  the  two 
specimens  at  the  same  temperature.  If  German  yeast  can 
not  be  obtained  readily,  about  a  teaspoonful  of  ordinary 
baker's  or  brewer's  yeast  may  be  used. 

Relations  of  the  Specific  Gravity  of  Urixe  to 
THE  Proportion  of  Sugar. — It  has  long  been  recognized 
that  the  specific  gravity  of  the  urine  bears  no  definite  and 
constant  relation  to  the  proportion  of  sugar  in  cases  of  dia- 
betes. In  a  case  that  came  under  my  observation  in  Decem- 
ber, 1883  and  has  been  under  treatment  until  the  time  of 
writing  (April,  1884)  on  Dec.  29,  1883.  the  specific  gravity 
was  1038,  with  28.4  grains  of  sugar  per  fluidounce.  The 
next  day.  the  specific  gravity  was  1036  and  the  proportion 
of  sugar  was  9  grains  per  fluidounce.  In  another  very 
interesting  case  now  under  treatment,  I  found  4  grains 
of  sugar  per  fluidounce,  the  urine  having  a  specific  gravity 
of  only  loii^.  These  remarkable  variations  in  the  spe- 
cific gravity,  occurring  without  any  relation  to  the  quan- 
tity of  sugar,  are  generally  dependent  upon  the  propor- 
tion of  urea,  the  absolute  quantity  of  which  is  often  very 
largely  increased  in  cases  of  diabetes.  I  have  often  found 
crystals  of  uric  acid  as  a  persistent  condition  in  diabetic 
urine,  sometimes  associated  with  a  deposit  of  oxalate 
of  lime. 

The  time  allotted  to  me  does  not  permit  a  discussion  of 
the  possible  relations  of  the  nutritive  conditions  connected 
with  diabetes  to  the  excessive  elimination  of  urea  or  th-^ 


328        TREATMENT    OF    DIABETES    MELLITUS 

frccjiicnt  presence  of  crystals  of  uric  acid;  but  it  is  very  im- 
portant to  remember  that  urine  of  a  comparatively  low 
specific  gravity  may  contain  sugar.  Within  a  week,  in 
another  case  in  which  the  urine  is  examined  every  three  or 
four  days,  I  found  a  marked  sugar-reaction  in  a  specimen 
of  urine  with  a  specific  gravity  of  loii.  I  have  also  re- 
peatedly found  sugar  in  urine  of  a  specific  gravity  of  about 
1 020,  the  quantity  of  urine  in  twenty-four  hours  being 
normal.  The  fact,  then,  that  the  quantity  and  specific 
gravity  of  the  urine  are  normal  does  not  in  itself  exclude 
sugar;  although,  in  most  cases  of  diabetes,  the  quantity 
of  urine  is  increased  and  its  specific  gravity  is  notably  high. 
In  a  case  of  dialjetes  very  minutely  reported  by  Pavy,  sugar 
was  found  in  the  urine  when  the  specific  gravity  of  the 
specimens  was,  on  different  occasions,  loio,  loii,  1012 
and  10 1 3.*  In  cases  in  which  diabetes  is  suspected,  the 
physician  is  not  justified  in  excluding  the  disease  when  he 
finds  no  increase  in  the  quantity  of  urine  and  a  normal  spe- 
cific gravity;  and  the  facts  just  mentioned  show  that  in  all 
cases  of  this  kind  the  urine  should  be  carefully  tested  for 
sugar. 

What  constitutes  Diabetes  Mellitus? — A  patient 
with  abnormal  thirst,  dryness  of  the  mouth,  suffering  from 
fatigue  following  slight  muscular  exertion,  progressively 
losing  strength  and  weight  and  passing  an  abnormally  large 
quantity  of  urine  of  high  specific  gravity  and  containing 
sugar  has  the  disease  known  as  diabetes  mellitus;  but  the 
various  symptoms  just  enumerated  may  exist  in  greater  or 
less  degree  or  some  of  them  may  be  absent.  In  addition  to 
these  symptoms,  others  may  exist ;  such  as,  abnormal  dry- 
ness of  the  skin,  deficient  perspiration  on  exercise  or  in 
"warm  weather,  pruritus  of  the  vulva,  a  tendency  to  furun- 
cles, unusual  lial^ility  to  "  take  cold,"  refluction  in  the  gen- 
eral temperature  of  the  body,  an  excessive  appetite,  failure 
of  the  generative  functions,  etc.,  but  these  are  not  neces- 
sarily present  in  cases  of  diabetes. 

On  the  other  hand,  none  of  the  general  symptoms  that 
I  have  mentioned  may  be  observed;  the  urine  may  be  nor- 
mal as  regards  quantity  and  specific  gravity;  but  still  sugar 
may  exist  constantly  in  small  quantity.     In  such  instances, 

*  Pavy,  "  Nature  and  Treatment  of  Diabetes,"  London,  1869,  p.  28S. 


TREATMENT    OF    DIABETES    MELLITUS        329 

which  are  not  infrequently  observed,  the  constant,  neces- 
sary and  invariable  symptom  of  diabetes  is  present;  namely, 
glycosuria.  Strictly  speaking,  perhaps,  patients  with  no 
general  symptoms,  with  no  increase  in  the  quantity  of  urine 
and  with  urine  of  normal  specific  gravity  may  be  said  to  be 
affected  with  glycosuria,  but  not  to  have  diabetes.  In  the 
great  majority  of  cases,  however,  unless  the  glycosuria  is 
transient  and  dependent  upon  some  recognizable  or  tem- 
porary cause,  certain  of  the  general  symptoms  of  diabetes 
will  sooner  or  later  become  developed,  unless  the  glycosuria 
is  relieved  by  treatment.  Still,  even  without  treatment, 
persons  may  live  in  what  seems  to  be  perfect  health  for 
years,  constantly  passing  considerable  quantities  of  sugar. 
I  can  now  call  to  mind  three  cases  of  this  kind;  and  several 
cases,  in  which  I  have  found  sugar  in  the  urine  without  any 
other  diabetic  symptoms,  have  passed  from  under  my  ob- 
servation. 

I  shall  have  little  to  say  concerning  the  etiology  and 
pathology  of  diabetes.  The  physiological  experiments, 
which  began  with  the  discovery  of  the  sugar-producing 
function  of  the  liver  by  Claude  Bernard,  in  1848,  have  failed, 
in  a  great  measure,  to  fulfil  the  expectation  that  they  would 
lead  to  a  full  comprehension  of  the  pathology  of  this 
disease.  I  believe  it  to  be  true  that  the  liver  is  a  sugar-pro- 
ducing organ.  The  experiments  of  Pavy,  in  which  he 
showed  that  the  liver-substance  does  not  actually  contain 
sugar  during  life  were,  in  my  opinion,  harmonized  with 
those  of  Bernard,  by  experiments  made  by  me  in  1869.* 
In  these  experiments,  I  found  no  sugar  in  an  extract  of  the 
liver  taken  from  a  living  dog  and  put  into  boiling  water  in 
ten  seconds,  while  sugar  was  present  in  blood  taken  from 
the  hepatic  veins.  I  am  convinced  that  the  liver  is  con- 
stantly forming  sugar  during  life;  but  that  this  sugar,  as  fast 
as  it  is  produced,  is  washed  out  of  the  sugar-producing 
organ  by  the  blood-current.  Experiments  have  shown, 
also,  that  the  sugar  contained  in  the  food  as  well  as  that 
resulting  from  the  digestion  of  starch  is  destroyed  in  the  or- 
ganism. That  the  sugar-forming  function  of  the  liver  may 
become  exaggerated  beyond  the  power  of  the  organism  to 

*  "  Experiments  undertaken  for  the  Purpose  of  reconciling  some  of  the  Dis- 
cordant  Observations  upon  the   Glycogenic    Function   of  the   Liver." — "  New 
"York  Medical  Journal,"  1S69,  vol.  viii.,  p.  373  et  seq. 
22 


330         TREATMENT    OF    DIABETES    MELLITUS 

destroy  the  excess  thus  formed  was  demonstrated  by  the 
remarka1)le  experiments  of  Bernard,  in  which  he  produced 
temporary  glycosuria  in  animals  by  mechanical  irritation  of 
the  floor  of  the  fourth  ventricle,  by  stimulating  the  pneu- 
mogastric  nerves  or  by  introducing  irritating  vapors  into 
the  lungs;  but  although  cases  of  traumatic  diabetes  occur 
in  the  human  subject,  they  are  exceedingly  rare.  No  such 
case  has  yet  come  under  my  observation. 

I  do  not  propose,  at  this  time  at  least,  to  offer  any 
theory  in  regard  to  the  causation  or  pathology  of  diabetes, 
the  cause  of  death  in  the  so-called  diabetic  coma  or  the  sup- 
posed development,  in  certain  cases,  of  acetonemia.  The 
discussion  of  these  points  has,  up  to  the  present  time,  been 
very  unsatisfactory.  It  is  well  known  that  patients  pre- 
senting in  a  well-marked  degree  certain  characteristic  symp- 
toms, in  addition  to  glycosuria,  are  affected  with  a  very 
grave  disease,  the  pathology  of  which  is  imperfectly  under- 
stood. The  sugar  resulting  from  digestion  is  in  great  part 
discharged  in  the  urine.  The  nutritive  processes  are  seri- 
ously disturbed.  The  power  of  resistance  to  other  diseases 
is  impaired;  and  what  is  remarkable  and  quite  interesting 
in  its  relations  to  our  ideas  of  the  production  of  animal  heat, 
the  failure  to  consume  the  carbohydrates  seriously  affects 
the  power  of  resistance  to  cold,  and  the  general  temperature 
of  the  body  is  habitually  95°  or  96°  Fahr.,  instead  of  about 
98^°.  This  latter  point  I  state  upon  the  authority  of  many 
writers;  and  in  a  case  now  under  treatment,  the  tempera- 
ture in  the  axilla  hag  constantly  been  about  96^°.  As  the 
patient  improved,  the  temperature  was  increased  to  a  frac- 
tion above  97°,  but  it  has  not  yet  reached  the  normal 
standard. 

Being  brought,  then,  face  to  face  with  a  disease,  very 
obscure  in  its  pathology  and  not  infrequent  in  its  occur- 
rence, the  practical  question,  to  which  I  intended  to  devote 
the  main  part  of  this  paper,  is  how  far  it  is  amenable  to 
treatment.  To  this  question  I  shall  devote  what  remains 
of  the  time  at  my  disposal. 

Treatment. — Tn  a  course  of  lectures  by  Cantani,  deliv- 
ered at  the  clinical  hospital  of  the  University  of  Naples,  in 
the  spring  of  1872,  there  occurs  the  following  statement, 
italicized  by  the  author: 

"  Diabetes  has  become  to-day  a  disease  easily  and  cer- 


TREATMENT    OF    DIABETES    MELLITUS         331 

taiiily  curable,  provided  that  the  treatment  (cure)  is  noi 
begun  too  late."  * 

The  cases  which  Cantani  details  in  support  of  this  rather 
startling  statement  show  certainly  most  remarkable  ef- 
fects of  treatment.  Judging  from  the  account  of  these 
cases,  the  general  proposition  that  diabetes  is  a  disease  in 
the  main  easily  and  certainly  curable  is  not  too  decided  and 
absolute.  Since  I  have  been  engaged  in  treating  cases  of 
this  disease,  my  experience,  though  not  extending  over 
many  years,  has  led  me  to  the  conviction  that  the  claim 
made  by  Cantani  is  not  entirely  extravagant. 

In  the  great  majority  of  cases  in  which  patients  will  sub- 
mit to  certain  measures  of  treatment  so  soon  as  it  is  estab- 
lished that  they  are  suffering  from  diabetes,  or  so  soon  as 
glycosuria  is  recognized,  it  is  possible  to  effect  either  a  cure 
of  the  disease  or  a  removal  of  most  of  the  characteristic 
svmptoms,  with  the  exception,  perhaps,  of  the  occasional 
appearance  of  a  small  quantity  of  sugar  in  the  urine. 

Time  does  not  permit  me  to  discuss  fully  the  treatment 
recommended  by  different  writers.  Cantani  relies  mainly 
upon  dietetic  measures,  although  he  attaches  considerable 
importance  to  the  exhibition  of  lactic  acid  and  the  alkaline 
lactates.  Of  course  the  treatment  by  eliminating  sugar  and 
starch  from  the  diet  is  by  no  means  novel.  Dating  from 
the  time  of  Rollo,  it  has  had  the  earnest  support  of  Bou- 
chardat,  Pavy,  Seegen  and  many  others.  I  desire  to  state 
at  the  outset,  that  the  main  and  almost  the  sole  reliance  of 
the  physician  should  be  upon  diet;  and  that  the  suppression 
of  starch  and  sugar  should  be  nearly  absolute.  Bearing  this 
constantly  in  mind,  in  considering  the  different  measures 
of  treatment  I  shall  divide  them  into  dietetic,  general,  and 
medicinal. 

Dietetic  Treatment. — In  1869,  a  patient  was  sent  to 
me  from  Omaha,  Neb.,  whpm  I  found  to  be  suffering  from 
many  of  the  distressing  symptoms  of  diabetes. 

On  November  20,  1869  he  passed  224  fluidounces  of 
urine  in  the  twenty-four  hours,  with  a  specific  gravity  of 
1035.  The  quantity  of  sugar  passed  in  the  twenty-four 
hours  was  18  ounces  and  30  grains,  and  the  quantity  of 
urea  was  624  grains.     I  recommended  a  diet-table  by  no 

*  Cantani,  "Le  diabete  Sucre  et  son  traitement  diet€tique,"  Paris,  1876,  p.  386. 


332        TREATMENT    OF    DIABETES    MELLITUS 

means  so  rigid  as  the  one  I  now  employ,  and  he  left  for 
home.  For  several  years  I  heard  from  this  patient,  either 
personally  or  through  his  physician  in  Omaha,  from  time 
to  time,  and  he  was  reported  as  apparently  well  but  occa- 
sionally passing  a  small  quantity  of  sugar.  He  continued 
the  diet  more  or  less  faithfully  for  two  or  three  years  but 
took  a  little  bread.  About  live  years  after,  I  was  accosted 
in  the  street  by  this  patient,  who  reported  himself  as  feel- 
ing perfectly  well  and  giving  but  little  attention  to  his 
diet.  At  this  time  I  did  not  have  an  opportunity  of  exam- 
ining the  urine.  The  patient  has  since  died;  and  I  heard 
from  his  widow  that  this  occurred  in  August,  1881,  his 
death  being  immediately  due  to  inflammation  of  the  bowels 
after  a  few  days'  illness.  ''  The  diabetes  was  much  im- 
proved and  troubled  him  very  little." 

This  case,  during  the  time  when  I  was  constantly  re- 
ceiving favorable  reports,  seemed  to  me  to  be  quite  remark- 
able; and  in  1880,  having  frequent  occasion  to  recommend 
a  diet  for  diabetics,  I  carefully  compiled  an  antidiabetic 
diet-table,  which  I  have  since  used  constantly  in  cases  that 
have  come  under  my  observation  and  which  I  shall  present 
as  an  appendix  to  this  paper.  In  preparing  this  table,  my 
object  has  been  to  secure  a  diet  sufficiently  nutritious  but 
free  from  starch  and  sugar,  using  as  a  basis  the  admirable 
list  given  by  Bouchardat;  '•'  and  I  have  endeavored  to  adapt 
the  articles  and  their  preparation  to  the  customs  of  our  own 
country,  adding  to  it,  when  possible,  in  order  to  secure  the 
greatest  available  variety  of  food.  Selecting,  however, 
every  dish  known  in  the  culinary  art,  without  reference  to 
the  trouble  or  expense  of  its  preparation,  a  rigid  diet  is  by 
no  means  easy  of  enforcement.  Patients  at  first  have  an 
intense  craving  for  bread;  and  this  desire  is  so  nearly  uni- 
versal that  almost  all  writers  on  diabetes  suggest  some  sub- 
stitute for  this  important  article  pf  food.  I  do  not  hesitate 
to  say,  however,  without  specifying  any  one  of  the  so- 
called  antidiabetic  breads  and  flours  as  especially  bad, 
that  all  the  articles  of  this  kind  in  our  markets  are  un- 
reliable and  most  of  them  fraudulent.  I  have  analyzed, 
or  caused  to  be  analyzed,  nearly  all  of  the  so-called 
bran-flours  and   gluten-flours  and  have  invariably  found 

*  Bouchardat,  "  De  la  glycosurie  ou  diabete  sucre,"  Pans,  1875,  p.  clxxxvi 


TREATMENT    OF    DIABETES    MELLITUS        333 

large  quantities  of  starch.  Two  specimens  said  to  be 
free  from  starch,  which  were  analyzed  with  great  care  by 
a  competent  chemist,  were  found  to  contain  a  greater  pro- 
portion than  exists  in  ordinary  wheat-flour.  Most  of  the 
so-called  diabetic  breads  are  pasty,  heavy  and  become  ex- 
tremely distasteful.  A  patient  now  under  occasional  ob- 
servation, having  procured  a  new  bread  w-hich  was  so  agree- 
able to  the  taste  that  he  took  it  freely  and  with  relish,  im- 
agined that  he  had  found  at  last  an  article  which  would  be 
regarded  by  diabetics  as  the  greatest  boon.  This  bread  was 
made  of  flour  which  contained  aljout  80  per  cent,  of  starch.* 
The  effects  of  this  fraud  upon  the  patient  were  quite  serious. 
His  health  had  become  nearly  restored  and  the  sugar  had 
disappeared  from  the  urine.  Under  the  use  of  the  bread 
the  sugar  returned  and  it  was  several  weeks  before  it  dis- 
appeared again  under  a  strict  diet.  In  the  rigid  dietetic 
treatment  bread  should  be  absolutely  interdicted;  or  in 
case  patients  should  refuse  to  submit  to  a  strict  diet,  a 
small  quantity  of  crust  of  bread  taken  with  an  abundance 
of  butter  may  be  allowed. 

A  rigid  diet,  without  bread,  should  be  continued  until 
the  sugar  has  disappeared  from  the  urine  and  all  the  diabetic 
symptoms  have  disappeared.  Although  many  diabetics 
rebel  under  this  regimen  and  the  execution  of  this  measure 
demands  on  their  part  much  self-denial  and  fortitude,  pa- 
tients may  be  encouraged  to  persevere,  by  the  statement 
that  the  craving  for  saccharine  and  starchy  articles  is  likely 
to  diminish  and  may  almost  disappear  after  a  few  weeks. 
I  have  now  under  observation  and  treatment  several  pa- 
tients who  have  actually  lost  all  desire  for  most  of  the  inter- 
dicted articles  of  food. 

In  cases  in  which  the  treatment  is  followed  by  an  appar- 
ent cure,  sugar  no  longer  existing  in  the  urine,  a  gradual  re- 
turn to  the  normal  diet  should  be  begun  about  two  months 
after  the  glycosuria  has  disappeared ;  but  it  is  of  the  greatest 
importance  during  this  part  of  the  treatment  to  keep  pa- 
tients, if  possible,  under  constant  observation,  examining 
the  urine  at  least  once  in  five  or  six  days.  When  the  sugar 
disappears,  patients  may  regard  themselves  as  permanent- 
ly cured  and  no  general  symptoms  present  themselves  for 

*  Ordinary  wheaten  flour  contains  about  70  per  cent,  of  starchy  matters. 


334        TREATMENT    OF    DIABETES    MELLITUS 

some  time  after  glycosuria  has  returned  vmder  a  mixed 
diet.  Several  unfortunate  examples  of  this  have  come 
under  my  observation. 

General  Treatment. — Measures  of  general  treatment 
are  to  be  directed  mainly  to  promoting  the  proper  action 
of  the  skin,  which  often  is  harsh  and  abnormally  dry,  and 
to  general  muscular  exercise.  Systematic  rubbing,  as 
practiced  by  massage,  and  Turkish  or  Russian  baths  once 
a  week,  if  not  contraindicated  by  some  complicating  con- 
ditions, are  useful.  A  reasonable  restriction  in  the  taking 
of  liquids  is  Cjuite  important  in  diminishing  the  quantity  of 
urine.  Under  dietetic  treatment  the  excessive  thirst  is  al- 
most always  relieved;  but  when  this  persists,  it  may  often 
be  temporarily  met,  so  far  as  dryness  of  the  mouth  is  con- 
cerned, by  taking  small  pieces  of  ice  from  time  to  time  in- 
stead of  drinking  water.  I  do  not  know  that  any  reliance 
is  to  be  placed  upon  the  use  of  the  various  mineral  waters 
that  are  said  to  exert  a  curative  influence  on  the  disease. 
Alcoholic  stimulants  are  to  be  avoided.  I  have  seen  several 
cases  of  diabetes  in  which  the  disease  seemed  to  be  attribu- 
table to  the  abuse  of  alcohol,  especially  the  habitual  and 
excessive  drinking  of  champagne.  In  certain  cases  some 
kind  of  alcoholic  1)everage  seems  to  be  necessary  to  main- 
tain the  vital  powers.  For  this  purpose,  a  fairly  good, 
sound  claret  has  seemed  to  me  to  be  the  best  form  in  which 
alcohol  may  be  taken.  Spirits  should  be  interdicted  or 
given  very  sparingly,  and  not  more  than  a  pint  of  claret 
should  be  taken  daily. 

Patients  sufifering  from  diabetes  lose  to  a  certain  ex- 
tent their  capacity  for  sustained  mental  effort.  They  should 
be  cautioned,  therefore,  against  excessive  intellectual  work. 
Mental  anxiety  and  "  worry  "  over  business  or  other  affairs 
exert  a  very  unfavorable  influence  on  the  progress  of  the 
disease.  In  some  cases  apparently  cured  I  have  noted  a 
return  of  the  glycosuria  which  seemed  to  be  fairly  attribu- 
table to  mental  causes.  Insomnia  rarely  demands  the  use 
of  narcotics  and  usually  is  relieved  with  the  other  symptoms 
by  the  antidiabetic  diet. 

The  various  minor  complications  that  are  liable  to  occur 
can  usually  be  overcome  by  appropriate  treatment.  Boils 
are  very  common  and  they  are  likely  to  be  persistent  and 
annoying.     When  the  tendency  to  boils  is  very  marked,  the 


TREATMENT    OF    DIABETES    MELLITUS         335 

sulphide  of  calcium  is  useful,  although  this  agent  does  not 
seem  to  exert  a  curative  influence  on  the  diabetic  con- 
dition. Sulphide  of  calcium  has  been  recommended  very 
highl}'  as  a  remedy  controlling  the  glycosuria;  but  it  often  is 
disagreeable  to  patients  and  disturbs  digestion.  In  a  few 
instances  in  which  I  have  employed  it  for  a  considerable 
time,  it  has  not  seemed  to  affect  the  discharge  of  sugar,  and 
I  regard  it  as  useful  only  to  combat  the  furuncular  tendency. 
It  is  dangerous  to  rely  upon  drugs  to  any  extent  in  the  treat- 
ment of  this  disease.  Patients  willingly  put  faith  in  rem- 
edies rather  than  in  a  rigid  diet;  but  after  all,  diet  is  the 
main  and  almost  the  only  reliance  in  treatment. 

Avery  important, and  perhaps  the  most  important  meas- 
ure of  general  treatment  is  systematic  muscular  exercise, 
not  carried  to  the  extent  of  producing  excessive  fatigue. 
This  may  be  taken  in  the  form  of  gymnastics  or  of  outdoor 
exercise,  such  as  riding  or  athletic  sports;  but  patients 
should  always  be  cautioned  to  avoid  "  taking  cold."  If  a 
patient  suffering  from  diabetes  can  be  made  to  develop 
his  muscular  strength  by  moderate  and  systematic  exer- 
cise, not  too  prolonged  and  followed  by  a  proper  and  not 
excessive  sense  of  fatigue  and  some  perspiration,  with  a 
good  reaction  after  bathing  and  rubbing,  much  will  be 
gained.  This  is  strongly  recommended  by  all  writers  upon 
diabetes. 

The  diminished  power  of  resistance  to  cold  which  exists 
nearly  always  in  diabetics  renders  it  necessary  to  enjoin 
great  care  to  avoid  exposure  to  the  vicissitudes  of  the 
weather,  and  the  constant  protection  of  the  body  by  warm 
clothing,  especially  flannels  next  the  skin. 

Medicinal  Treatment. — There  is  no  remedy  that 
exerts  a  curative  influence  over  diabetes  in  the  absence  of 
proper  dietetic  measures.  Opium,  the  bromides,  sulphide 
of  calcium,  various  mineral  waters  and  other  medicinal 
agents  that  have  been  recommended  from  time  to  time  have 
all  proved  unsatisfactory  in  practice.  Of  course  it  is  dififi- 
cult  to  estimate  the  value  of  drugs  in  this  as  in  many  other 
diseases,  particularly  as  the  physician  is  not  justified,  in  my 
opinion,  in  neglecting  to  enforce  a  rigid  diet  which  in  itself, 
in  the  great  majority  of  cases,  exerts  a  decided  influence 
over  the  glycosuria  and  the  general  symptoms.  On  the- 
oretical grounds,  Cantani  recommends  lactic  acid,  taken  in 


336        TREATMENT    OF    DIABETES    MELLITUS 

the  form  of  a  ''  lemonade,"  in  small  quantities  throughout 
the  day.     The  formula  for  this  mixture  is  the  following: 

Pure  lactic  acid 3  iss  to  3  v. 

Aromatic  water 3  v  to  ^  j. 

Water. , Oij. 

This  remedy  is  regarded  by  Cantani  as  useful  in  many 
cases  but  not  essential.     I  have  little  experience  in  its  use. 

Keeping  in  mind  the  small  reliance  to  be  placed  on  the 
efificacy  of  drugs  not  conjoined  with  dietetic  measures,  I 
must  bear  testimony  to  the  apparent  advantage  to  be  de- 
rived from  the  use  of  the  bromide  of  arsenic,  recently  pro- 
posed by  Clemens.  While  I  have  not  felt  justified  in  using 
this  remedy  to  the  exclusion  of  an  antidiabetic  diet,  for  the 
reason  that  the  bad  effects  of  an  unrestricted  diet  frequently 
persist  for  some  time,  I  have  noted  very  marked  effects 
from  Clemens'  solution  in  controlling  the  discharge  of 
sugar  and  some  of  the  distressing  symptoms,  particularly 
the  excessive  thirst ;  so  that,  aside  from  simple  measures  to 
relieve  sleeplessness,  constipation  or  other  intercurrent  dififi- 
culties,  I  have  lately  been  in  the  habit  of  prescribing,  in  ad- 
dition to  the  diet,  three  drops  of  Clemens'  solution,  three 
times  daily,  in  a  wine-glass  of  water  after  each  meal,  gradu- 
ally increasing  the  dose  to  five  drops.  The  following  is  the 
formula  for  this  remedy: 

"  Liquor  brom-arsen  consists  simply  of  a  chemical 
union  of  arsenious  acid  and  bromine,  dissolved  in  water 
and  glycerin,  in  such  a  manner  that  two  drops  represent 
the  twenty-fourth  part  of  a  grain  of  arsenite  of  bromine."* 

In  a  case  of  diabetes  of  more  than  five  years'  standing, 
now  under  treatment,  the  patient  has  been  taking  Clemens'' 
solution  constantly,  with  the  exception  of  a  single  week, 
from  Dec.  2'/,  1882  to  April  2,  1884,  more  than  fifteen 
months,  without  unpleasant  effects.  I  began  with  a  dose 
of  two  drops  three  times  daily,  gradually  increased  to  five 
drops.  On  May  13,  1883,  the  urine  having  been  free  from 
sugar  with  the  exception  of  a  trace  on  two  or  three  occa- 
sions for  thirteen  weeks,  I  stopped  the  bromide  of  arsenic 
for  one  week,  the  antidiabetic  diet  being  continued.  At 
the  end  of  the  week  sugar  was  found  in  large  quantity  in 
the  urine.    The  use  of  the  bromide  of  arsenic  was  then  re- 

*  "  Medical  Times,"  Philadelphia,  Dec.  2,  1882,  p.  160. 


TREATMENT    OF    DIABETES    MELLITUS        337 

sumed.  At  the  end  of  the  first  week  the  sugar  still  existed 
in  small  quantity.  At  the  end  of  the  second  week  the  sugar 
had  disappeared  and  there  was  no  return  for  six  weeks. 
The  patient  then  left  the  city  and  committed  many  indiscre- 
tions in  diet.  Seven  weeks  later  I  examined  a  specimen  of 
urine  and  found  it  loaded  with  sugar,  with  a  specific  gravity 
of  1030.  While  abseiit  from  New  York,  the  patient  had 
indulged  in  peas,  egg-plant,  stuffed  tomatoes,  green  corn, 
ice-cream,  charlotte  russe,  peaches,  raspberries,  blackberries 
and  melons.  On  September  20,  after  returning  to  New 
York  and  resuming  a  strict  diet  with  the  exception  of  the 
crust  of  half  a  white  roll  three  times  daily,  the  patient  im- 
proved. The  urine  on  September  20  had  a  specific  gravity 
of  103 1  and  w-as  loaded  with  sugar.  The  following  week 
the  sugar  was  much  diminished  in  quantity  and  it  dis- 
appeared at  the  end  of  the  second  week. 

Summary  of  Treatment. — The  more  I  study  the  cases 
of  diabetes  that  have  come  under  my  observation,  especially 
those  that  are  now  under  treatment,  in  connection  w4th  the 
writings  of  those  who  have  faithfully  followed  the  dietetic 
plan,  notably  Bouchardat  and  Cantani,  the  more  thoroughly 
am  I  convinced  that  the  prognosis  in  a  recent  and  un- 
complicated case  of  this  disease  in  an  adult  is  favorable, 
provided,  always,  that  the  proper  measures  of  treatment 
are  rigidly  enforced.  In  the  hone  of  convincing  the  profes- 
sion that  this  statement  is  reliable,  I  shall,  at  the  risk  of  what 
may  appear  to  be  needless  repetition,  give  a  summary  of 
treatment,  with  brief  statements  of  the  progress  of  cases 
that  I  am  now  actually  observing. 

At  the  outset  patients  should  be  impressed  with  the 
fact  that  they  are  suffering  from  a  grave  disorder  and  that 
everything  depends  upon  their  full  cooperation  in  the  treat- 
ment, which  treatment  is  essentially  dietetic.  The  diet- 
table  should  be  carefully  studied  and  the  diet  regulated  and 
carried  out  absolutely. 

In  case  a  rigid  antidiabetic  diet  does  not  promptly  in- 
fluence the  glycosuria,  it  may  be  well  to  subject  a  patient 
to  an  absolute  fast  for  twenty-four  hours  and  follow  this 
with  the  antidiabetic  regimen.  This  rather  harsh  measure 
is  suggested  by  Cantani.  I  shall  not  hesitate  to  employ  it 
in  cases  in  which  it  may  seem  to  be  required,  although  no 
such  case  has  as  yet  come  under  my  observation. 


338        TREATMENT    OF    DIABETES    MELLITUS 

The  various  measures  that  I  have  mentioned  under  the 
head  of  "  General  Treatment  "  should  be  enforced,  es- 
pecially systematic  daily  muscular  exercise.  A  moderate 
system  of  training  on  the  plan  adopted  by  athletes  is  useful; 
and  this,  if  continued,  will  do  much  to  render  a  cure  per- 
manent after  return  to  a  normal  diet. 

The  return  to  a  normal  diet  should  be  gradual,  and 
(luring  this  time  the  urine  should  be  examined  frequently, 
the  rigid  diet  being  resumed  at  the  first  reappearance  of 
sugar  in  the  urine;  but  all  alcoholic  excesses,  the  immoder- 
ate use  of  sweet  fruits  and  any  use  of  sugar  should  be  inter- 
dicted at  all  times.  A  patient  who  has  once  had  diabetes 
is  always  liable  to  a  return  of  the  disorder.  He  must  lead 
a  thoroughly  careful,  hygienic  and  temperate  life.  In  the 
words  of  Bouchardat,  "  you  will  not  be  cured  except  on 
the  condition  that  you  never  believe  yourself  to  be 
cured."  * 

While  I  believe  that  the  physician  is  justified  in  en- 
couraging patients  to  expect  relief,  and  even  cure,  in  recent, 
uncomplicated  cases,  the  diet  is  all  important;  and  its  regu- 
lation can  not  be  expected  to  be  perfect  without  profes- 
sional aid  in  its  enforcement.  A  diabetic  is  never  safe  from 
a  return  of  his  disease,  even  when  he  believes  himself  to  be 
cured;  and  under  no  circumstances  should  he  pass  more 
than  a  few  weeks  without  an  examination  of  the  urine. 

The  bromide  of  arsenic,  or  Clemens'  solution,  appears 
to  be  useful.  Patients  may  begin  with  three  drops  three 
times  daily  in  a  little  water  immediately  after  eating,  grad- 
ually increasing  the  dose  to  five  drops.  This  may  be  con- 
tinued for  weeks  and  months  without  producing  any  un- 
favorable effects;  but  the  administration  of  this  remedy 
does  not  supply  the  place  of  the  dietetic  treatment,  which 
should  be  enforced  in  all  cases.  A  rigid  diet  should  be 
continued  for  two  months  at  least,  even  in  the  mildest 
cases  of  the  disease.  It  may  be  necessary  in  certain  cases 
to  continue  it  for  a  longer  period,  even  twelve  or  more 
months. 

There  is  probably  no  such  disease  as  intermittent  dia- 
betes. In  some  instances  glycosuria  occurs  during  the  sea- 
son of  sweet  fruits,  when  they,  are  indulged  in  excessively, 

*  Bouchardat,  "  De  la  glycosuria  ou  diabete  sucre."  Paris,  1875,  p.  49. 


TREATMENT    OF    DIABETES    MELLITUS         339 

and  disappears  when  the  diet  is  changed;  but  these  are  mild 
cases  of  diabetes,  excluding  those  in  which  a  transient  gly- 
cosuria follows  the  inhalation  of  irritating  vapors,  the  tak- 
ing of  anesthetics,  etc. 

Robust  or  corpulent  persons  are  more  tolerant  of  the 
disease  than  those  who  are  feeble  or  spare;  and  the  glyco- 
suria yields,  in  such  cases,  more  readily  to  treatment. 

Diabetes  occurs  at  all  ages.  Bouchardat  mentions  a 
case  in  an  infant  of  three  years,  although  the  disease  is 
rare  before  the  age  of  twelve.  The  most  unfavorable  cases 
are  those  which  occur  before  the  age  of  puberty.  An  adult 
male  presents  the  most  favorable  conditions  for  cure.  In 
old  persons,  when  the  disease  is  of  long  standing,  the  die- 
tetic treatment  will  secure  practical  immunity  from  nearly 
all  the  distressing  symptoms,  although  the  glycosuria  may 
not  be  entirely  removed. 

A  study  of  any  of  the  diet-tables  recommended  will 
make  it  evident  that  those  who  are  able  to  follow  the  re- 
quired regimen,  without  regard  to  the  cost  of  articles  of 
food,  present  much  more  favorable  conditions,  as  regards 
the  prospect  of  cure,  than  persons  in  straitened  or  indi- 
gent circumstances.  Diabetes,  however,  occurs  in  all 
classes  and  is  by  no  means  a  rare  disease.  A  hospital  de- 
voted to  such  cases,  w^here  the  dietetic  treatment  could 
be  strictly  carried  out,  would  be  a  boon  to  the  rich  and 
poor  alike. 

Cases. — I  have  accounts,  more  or  less  complete,  of  fifty 
cases  of  diabetes.  Certain  of  these  cases  have  been  lost 
sight  of;  others  were  followed  out  in  their  histories  to  a 
fatal  termination;  and  tw^elve.  exclusive  of  a  few  that  are 
reported  to  be  cured,  are  still  under  either  observation 
or  treatment. 

Of  these  fifty  cases,  sixteen  have  been  lost  sight  of.  nine- 
teen are  either  known  to  be  living  or  are  under  observation, 
and  twelve  have  died  at  periods  of  between  nine  months 
and  twelve  years  after  I  first  examined  the  urine. 

Of  the  seven  patients  who  are  living  but  whom  I  do  not 
consider  as  under  observation,  one  passes  sugar  constantly 
and  is  under  an  imperfect  antidiabetic  diet,  but  is  in  w4iat 
may  be  called  fair  health;  two  are  reported  as  cured,  al- 
though I  have  not  examined  the  urine  for  a  long  time;  four 
I  simply  know  to  be  living. 


340        TREATMENT    OF    DIABETES    MELLITUS 

The  twelve  cases  that  are  under  ol:)servation  are  instruct- 
ive as  indicating  the  value  and  influence  of  treatment. 

Case  A. — The  patient,  a  gentleman  thirty-eight  years  of  age, 
first  became  aware  that  he  sutTercd  from  diabetes  mellitus  about 
June  I,  1883.  He  is  five  feet  five  inches  in  height  and  weighs  one 
hundred  and  twenty-nine  pounds.  A  year  ago  he  weighed  one 
hundred  and  sixty  pounds.  He  suffered  from  excessive  discharge 
of  urine,  with  increased  appetite,  thirst,  dryness  of  the  mouth,  sleep- 
lessness, fatigue  on  slight  exercise,  and,  indeed,  most  of  the  symp- 
toms of  diabetes;  but  a  careful  physical  examination  failed  to  re- 
veal any  other  disease.  At  the  time  I  first  saw  him,  he  had  been 
taking  quinine  and  various  tonic  remedies  and  had  been  subjected 
to  an  imperfect  antidiabetic  diet.  At  this  time,  December  29,  1883,. 
he  passed  eighty  ounces  of  urine  in  twenty-four  hours,  containing 
in  all  3,072  grains  of  sugar.  He  was  immediatelv  put  upon  a  strict 
diet,  taking  no  bread,  drinking  very  little,  and  relieving  the  thirst 
temporarily  by  taking  pieces  of  ice.  In  addition,  he  took  three 
drops  of  Clemens'  solution  three  times  daily,  and  continued  tO' 
take  ten  grains  of  quinine  each  day.  After  forty-eight  hours  of  this 
treatment,  his  intense  thirst  and  excessive  urination  disappeared; 
but  he  expressed  himself  as  feeling  rather  weak  although  generally 
much  better.  The  effect,  however,  upon  the  discharge  of  sugar  was 
remarkable.  He  passed,  during  the  second  twenty-four  hours  of 
treatment,  forty-three  ounces  of  urine,  and  the  total  quantity  of 
sugar  was  reduced  from  3,072  grains  to  387  grains. 

I  heard  from  this  patient  January  19,  1884,  and  received  a 
specimen  of  the  urine  of  the  twenty-four  hours  of  January  17th. 
For  the  twenty  days  since  December  29,  1883,  he  had  maintained 
an  absolute  antidiabetic  diet,  taking  no  bread.  During  this  time 
he  took  three  drops  of  Clemens'  solution  three  times  daily.  He 
had  gained  three-quarters  of  a  pound  in  weight.  He  had  suffered 
somewhat  from  indigestion  but  was  otherwise  quite  well.  "  The 
very  large  appetite  and  thirst  are  very  materially  lessened."  The 
quantity  of  urine  in  twenty-four  hours  was  forty-eight  and  one-half 
fluidounces ;  specific  gravity,  1026;  absolutely  no  sugar;  there  was 
rather  an  abundant  deposit  of  amorphous  urates  with  a  number  of 
crystals  of  uric  acid.  So  far  as  the  diabetic  condition  is  con- 
cerned, the  general  symptoms  have  disappeared  as  well  as  the  sugar 
in  the  urine. 

On  January  25,  1884,  the  dose  of  Clemens'  solution  was  in- 
creased to  five  drops  three  times  daily.  The  urine  was  free  from 
sugar.  There  was  no  sugar  in  the  urine  on  January  27  and  29. 
He  was  then  allowed  the  crust  of  half  a  French  roll  at  breakfast. 

On  February  4,  1884,  I  saw  the  patient  again.  He  had  been 
at  home  and  had  committed  some  slight  indiscretions  in  diet.  The 
urine  had  a  specific  gravity  of  1030  and  contained  a  small  quantity 
of  sugar.     The  strict  diet  was  resumed. 

On  February  10,  1884,  there  was  a  trace  of  sugar  in  the  urine. 

On  February  24,  1884,  the  patient  still  under  a  strict  diet  and 
the  use  of  Clemens'   solution,  there  was  no   sugar  in  the  urine. 


TREATMENT    OF    DIABETES    MELLITUS        341 

The  patient  went  home,  feehng  perfectly  well,  and  promised  to 
send  a  specimen  of  urine  in  two  weeks.  At  no  time  since  the  be- 
ginning of  treatment  was  there  any  excessive  quantity  of  urine.* 

Case  B. — The  patient  is  a  gentleman  fifty-seven  years  of  age, 
five  feet  eleven  and  one-half  inches  in  height,  weighing  one  hun- 
dred and  seventy-two  pounds.  He  had  suffered  from  diabetes  to  his 
knowledge  for  about  one  year,  with  thirst,  fatigue  after  moderate 
exertion  and  other  mild  symptoms.  He  had  been  under  a  moderate 
antidiabetic  diet  for  some  weeks.  After  he  came  under  my  ob- 
servation, his  urine,  under  a  strict  antidiabetic  diet,  was  either 
entirely  free  from  sugar  or  contained  merely  a  trace,  for  ten  months. 
He  had  no  symptoms  and  regarded  himself  as  cured.  For  about 
three  months  he  took  four  drops  of  Clemens'  solution  three  times 
daily. 

On  January  17,  1884,  he  presented  himself,  passing  a  large 
•quantity  of  urine  of  a  specific  gravity  of  1027  and  loaded  with 
sugar.  Having  regarded  himself  as  permanently  cured,  he  had 
returned  to  his  old  diet,  including  sugar,  and  had  stopped  the 
bromide  of  arsenic  for  six  months.  He  felt  perfectly  well  but  had 
noticed  for  some  days  that  he  was  passing  a  large  quantity  of 
urine.  He  was  again  put  upon  an  antidiabetic  diet  (which  I 
fear  was  not  strictly  followed)  with  six  drops  of  Clemens'  solu- 
tion twice  daily.  On  February  7,  1884  he  passed  a  normal 
quantity  of  urine  of  a  specific  gravity  of  1022,  containing  but  a 
trace  of  sugar. 

In  this  case,  I  can  not  secure  strict  attention  to  the  diet  and 
regular  examinations  of  the  urine. f 

Case  C. — This  patient  has  been  under  observation  since  Octo- 
ber, 1880.  He  was  at  that  time  fifty-three  years  of  age,  five  feet 
eight  and  one-half  inches  in  height  and  weighed  one  hundred  and 
sixty-eight  to  one  hundred  and  seventy-two  pounds.  Glycosuria 
had  been  recognized  a  few  weeks  before  he  came  under  my  ob- 
servation; and  he  had  been  subjected  to  an  imperfect  antidiabetic 
diet.  He  was  immediately  put  upon  a  strict  diet,  and  from  Octo- 
ber 21,  1880  to  May  18,  1881,  his  urine  generally  contained  no 
sugar,  although  there  was  occasionally  a  trace.  In  this  case  the 
diet  was  strictly  followed,  and  the  patient  soon  lost  his  desire  for 
prohibited  articles,  even  bread. 

On  May  18,  1881  he  was  allowed  the  fruits  in  season  to  be 
taken  without  sugar.  On  June  27  he  was  allowed  a  little  bread. 
His  urine  was  practically  free  from  sugar  until  February  17,  1882, 
with  the  exception  of  an  occasion  on  November  5,  1882,  when  it 
had  a  specific  gravity  of  1029  and  contained  considerable  sugar 
following  a  slight  excess  at  table  in  taking  claret  and  whisky  and 
w^ater. 

*  On  April  29,  1884  I  received  a  specimen  of  urine  from  this  patient.  The 
quantity  in  twenty-four  hours  was  said  to  be  about  fifty  fluidounces.  The  spe- 
cific gravity  was  I022^  and  contained  a  trace  of  sugar.  The  general  health 
was  reported  as  perfect. 

+  I  saw  this  patient  on  April  29,  1884,  and  he  reported  himself  as  perfectly 
well,  but  I  did  not  have  an  opportunity  of  examining  the  urine. 


342         TREATMENT    OF    DIABETES    MELLITUS 

On  February  17.  1882  his  urine  had  a  specific  {gravity  of  1026 
and  contained  considerable  sugar.  He  had  been  living  rather  freely 
for  some  time  without  committing  any  actual  excesses  at  table. 
He  moderated  his  living  and  was  given,  in  addition  to  the  strict 
diet,  one-quarter  of  a  grain  of  sulphide  of  calcium  three  times 
daily.  From  February  17,  1882  to  September  i,  1883  his  urine 
was  practically  free  from  sugar  when  examined  on  ten  different 
occasions,  once,  only,  presenting  a  mere  trace.  During  the  entire 
treatment  he  has  taken  considerable  exercise  in  walking.  He  took 
the  sulphide  of  calcium  rather  irregularly  for  six  months,  but  it 
was  very  disagreeable. 

On  January  11.  1883  he  began  to  take  the  bromide  of  arsenic, 
which  he  continued  rather  irregularly. 

On  January  23,  1884  his  weight  had  increased  to  175^  pounds. 
Since  September  i,  1883  his  diet  had  been  practically  unrestricted. 
His  urine  had  a  specific  gravity  of  1021  and  contained  a  small 
quantity  of  sugar.  He  was  put  on  a  moderate  antidiabetic  diet  and 
the  dose  of  bromide  of  arsenic  was  increased  to  five  drops.  On 
February  7,  1884  the  sugar  was  still  marked  in  the  urine,  but  he 
indulged  rather  too  freely  in  claret  at  dinner  and  drank  some  brandy 
and  soda  during  the  evening.  From  February  7,  to  April  3,  1884 
the  urine  had  been  nearly  always  free  from  sugar. 

This  may  be  called  almost  a  case  of  cure.  For  the  greatest 
part  of  the  time  from  October,  1880  to  April,  1884,  three  and  one- 
half  years,  the  urine  has  been  practically  free  from  sugar,  for  some 
of  the  time  under  an  ordinary  diet.  During  this  period  sugar  has 
appeared  temporarily  and  in  small  quantity,  possibly  as  a  conse- 
quence of  occasional  indiscretions  in  the  use  of  wine,  which  could 
not  by  any  means  be  regarded  as  excesses  in  a  person  in  ordinary 
health.* 

Case  D. — This  is  the  case  of  a  lady,  rather  stout,  fifty-nine 
years  of  age,  who  came  to  me  for  treatment  in  December,  1882. 
The  patient  has  already  been  referred  to  in  connection  with  the 
fact  of  the  existence  of  sugar  in  urine  of  a  low  specific  gravity, 
(loiij)  and  the  return  of  glycosuria  immediately  following  the 
suspension  for  one  week  of  the  administration  of  bromide  of  ar- 
senic. 

In  December,  1880  the  patient  was  in  a  deplorable  condition, 
suffering  from  some  of  the  most  distressing  symptoms  of  diabetes. 
She  suffered  intensely  from  thirst,  night  and  day,  and  was  forced 
to  pass  urine  nearly  every  hour.  She  also  suffered  greatly  from 
pruritus  vulvae.  Her  disease  was  of  five  years'  standing,  and  she 
had  been  subjected  to  various  forms  of  treatment,  but  never  to 
a  strict  diet.  She  had  consulted  many  distinguished  physicians  in 
this  country  and  in  Europe. 

On  December  16,  1882  she  passed  128  ounces  of  urine,  of  a 
specific  gravity  of  1036,  containing  twenty-two  grains  of  sugar  per 

*  On  April  28,  1884  this  patient  reported  himself  as  perfectly  well.  His 
urine  had  a  specific  gravity  of  1020^  and  contained  no  sugar.  The  diet  had 
been  not  absolutely  strict,  but  was  what  may  be  called  moderately  antidiabetic. 


TREATMENT    OF    DIABETES    MELLITUS        343 

fluidounce,  or  2,816  grains  in  the  twenty-four  hours.  The  next  day 
she  was  put  upon  a  strict  antidiabetic  diet. 

On  December  22,  1882  the  daily  quantity  of  urine  was  reduced 
to  fifty-two  ounces,  with 'a  specific  gravity  of  1026  and  containing 
eight  grains  of  sugar  per  fluidounce,  or  four  hundred  and  sixteen 
grains  in  the  twenty-four  hours.  The  urine  constantly  presented 
crystals  of  uric  acid.  The  thirst,  pruritus  and  constant  desire  to 
pass  urine  were  relieved. 

With  the  exception  of  one  week,  this  patient  took  Clemens' 
solution,  two  drops  three  times  daily,  the  dose  finally  increased  to 
five  drops,  from  December  27,  1882  to  April  2,  1884.  The  treatment 
during  this  period  consisted  of  the  diet  and  Clemens'  solution,  with 
occasional  remedies  to  act  upon  the  bowels.  She  has  been  almost 
constantly  under  treatment,  and  I  made  ninety-one  examinations 
of  the  urine  up  to  April  6,  1884.  Her  urine  is  now  examined 
regularly  once  a  week. 

Under  treatment  the  quantity  of  sugar  in  the  urine  diminished 
until  the  glycosuria  disappeared  January  2y,  1883,  about  thirty 
days  after  the  first  examination.  From  January  27,  1883  to  April 
6,  1884,  with  the  exception  of  about  six  weeks  passed  at  a  watering- 
place  in  the  summer  of  1883,  under  very  unfavorable  conditions  as 
regards  diet,  the  urine  has  either  been  free  from  sugar  or  has  con- 
tained a  very  small  quantity.  The  quantity  of  urine  has  been  nor- 
mal, and  the  general  diabetic  symptoms  have  never  reappeared. 
She  now  uses  the  antidiabetic  diet  with  the  crust  of  one-half  of 
a  French  roll  at  each  meal,  a  pint  of  cream  daily  and  a  little  fruit 
in  season. 

While  this  can  not  be  called  an  instance  of  cure,  the  fact  that 
the  patient  lives  comfortably  and  in  apparently  good  health  under 
a  diet  that  is  not  particularly  irksome  shows  that  cases  of  long 
standing  and  presenting  very  unfavorable  features  are  by  no  means 
hopeless.  This  case  presented  in  a  remarkable  degree  the  example 
of  a  loss  of  desire  for  prohibited  articles  of  food.  She  now  looks 
forward  to  eating  melons  in  season,  which  is  about  the  only  decided 
wish  she  has  expressed  for  food  not  suited  to  her  condition.* 

Case  E. — The  patient  in  this  case  is  a  gentleman  about  fifty 
years  of  age,  living  in  Ohio.  I  examined  his  urine  May  24,  1878 
and  November  17,  1881.  for  some  reason  not  connected  with  a  sus- 
picion of  diabetes  and  found  no  sugar.  On  May  4.  1882  I  again 
examined  the  urine,  on  account  of  certain  diabetic  symptoms,  and 
found  a  large  quantity  of  sugar.  He  was  at  once  put  on  the  anti- 
diabetic diet,  which  he  attemnted  to  carry  out  by  himself  at  his 
home  in  Ohio.  In  January,  1884  he  reported  that  all  his  symptoms 
had  been  relieved  and  that  he  suffers  nothing  unless  he  commits 
indiscretions  in  diet. 

*  The  urine  of  this  patient  is  examined  regularly  once  a  week,  and  there 
has  been  no  sugar,  with  the  exception  of  a  trace  on  one  occasion,  for  twelve 
weeks.  The  last  examination  was  made  on  ^lay  4,  1884,  and  no  sugar  was 
found.  With  the  exception  of  sugar,  the  diet  has  been  but  little  restricted  for 
three  weeks.  For  the  last  three  weeks  the  patient  has  been  taking  about  a  pint 
daily  of  the  lactic  acid  drink  recommended  by  Cantani. 


344    .    TREATMENT    OF    DIABETES    MELLITUS 

Case  F. — The  patient  in  this  case  is  a  j^cntleman  about  fifty 
years  of  age  and  of  medium  muscular  and  adipose  development. 
Having  been  suffering  for  some  months  from  diabetic  symptoms, 
his  urine  was  examined  by  me  on  March  22,  1878.  I  then  found 
a  specific  gravity  of  1022  and  a  large  (|uantity  of  sugar.  He  was 
at  once  put  upon  a  moderate  antidiabetic  diet. 

On  April  26,  1878  I  found  the  urine  normal  and  the  diabetic 
symptoms  had  disappeared.  Between  April  26,  1878  and  January 
ID,  1882  I  examined  the  urine  seven  times,  always  finding  it  normal. 
On  October  14,  1882  he  passed  ninety-six  ounces  of  urine  in 
the  twenty-four  hours,  with  a  specific  gravity  of  1027  and  contain- 
ing four  grains  of  sugar  per  fluidounce.  His  diet  for  some  time 
had  been  irregular,  and  he  had  depended  on  various  remedies,  such 
as  the  bromides  and  the  sulphide  of  calcium.  He  then  began  to 
take  the  bromide  of  arsenic,  but  his  diet,  though  moderately  anti- 
diabetic, was  still  imperfectly  regulated.  His  urine,  examined 
February  20,  May  18  and  May  28,  1883,  contained  a  small  quantity 
of  sugar.  On  August  15,  1883  I  examined  the  urine  and  found  a 
trace  of  sugar.* 

This  patient  suffers  very  little  from  diabetic  symptoms.  I  have 
little  doubt  that  the  glycosuria  could  be  arrested  by  a  few  weeks 
of  strict  dietetic  treatment. 

Case  G. — The  patient  is  a  lady,  rather  stout,  and  about  seventy- 
five  years  of  age.  Attention  was  directed  to  the  urine  on  Febru- 
ary 7,  1884,  by  excessive  thirst  and  urination,  with  pruritus  vulvae. 
Before  I  examined  the  urine  it  was  reported  to  me  that  she  was 
passing  it  in  large  quantity,  the  specific  gravity  being  1040,  and 
that  it  was  loaded  with  sugar.  Under  an  antidiabetic  diet  and  the 
bromide  of  arsenic,  in  three  days  the  quantity  of  urine  was  reduced 
to  the  normal  standard  and  the  diabetic  symptoms  disappeared.  I 
examined  the  urine  on  February  13,  19,  28,  March  4,  11,  17,  21,  25, 
31,  and  April  5,  1884.  The  urine,  with  one  exception,  presented 
sugar  in  small  but  variable  proportions ;  but  its  quantity  usually 
was  normal,  and  the  specific  gravity  varied  between  1007  and  1020. 
The  urine  on  one  occasion,  with  a  specific  gravity  of  loio,  con- 
tained a  trace  of  sugar.  On  March  17,  the  urine  had  a  specific 
gravity  of  1007  and  contained  no  sugar.  The  general  diabetic 
symptoms  are  now  entirely  relieved.  The  only  fault  in  the  diet  is 
that  the  patient  takes  a  quart  of  milk  daily.  The  progress  of  this 
•case  is  quite  favorable  up  to  the  present  time. 

Case  H. — The  patient  is  a  large  and  rather  corpulent  man  about 
sixty  years  of  age.  I  examined  the  urine  December  27,  1882  and 
found  it  with  a  specific  gravity  of  1027  and  containing  a  consider- 
able quantity  of  sugar.  He  was  at  once  put  upon  an  antidiabetic 
diet.  Under  this  treatment  the  glycosuria  and  other  diabetic  symp- 
toms disappeared.     In  July,  1883  he  was  attacked  with  hemiplegia, 

*  From  April  5  to  May  2,  1884  I  made  six  examinations  of  the  urine. 
The  specific  gravity  has  been  between  1012^  and  1020  and  a  small  quantity  of 
sugar  has  always  been  noted  ;  but  there  have  been  no  general  diabetic  symp- 
toms.    The  diet  has  not  been  rigidly  carried  out. 


TREATMENT    OF    DIABETES    MELLITUS        345 

from  which  he  has  substantially  recovered.  He  was  reported  in 
March,  1884  as  perfectly  well,  having  returned  to  the  normal  diet.* 

Cases  I,  J,  K,  and  L. — These  are  cases  of  patients  who  are 
constantly  passing  sugar  in  large  quantities,  under  little  or  no  treat- 
ment, but  who  enjoy  fair  health.  In  one  of  these  cases  the  patient 
obstinately  refuses  to  regulate  the  diet ;  and  although  he  suffers 
but  little  from  diabetic  symptoms,  he  has  become  greatly  reduced 
in  weight  and  strength  wathin  the  past  two  years.  A  yovmg  daugh- 
ter of  this  patient,  whom  I  saw  repeatedly  and  who  never  followed 
out  an  antidiabetic  diet,  died  of  diabetes  about  three  years  ago. 
Another  patient  has  fair  health  under  a  rather  irregular  diet.  He 
is  so  situated  as  to  be  unable  to  carry  out  a  strict  regimen.  The 
two  other  patients  are  large  and  corpulent  men,  who  pass  immense 
quantities  of  sugar,  with  no  restriction  in  diet  or  in  drinking. 

Of  the  fifteen  cases  of  death  the  reports  are  generally  imper- 
fect. Four  are  reported  as  having  died  of  diabetes ;  one,  of  dia- 
betic coma,  possibly  acetonemia;  three,  of  albuminuria;  one,  of 
apoplexy ;  one,  of  hemoptysis ;  one,  of  "  inflammation  of  the  bow- 
els " ;  and  in  the  remaining  four  cases  I  have  not  been  able  to  learn 
■  the  cause  of  death. 

Case  M. — I  have  already  referred  to  this  case.  The  patient 
was  a  stout,  heavy  man  about  forty  years  of  age.  I  examined  him 
November  20,  1869.  He  then  passed  224  ounces  of  urine  in  the 
twenty-four  hours,  with  a  specific  gravity  of  1035,  containing  18 
ounces  and  30  grains  of  sugar  and  624  grains  of  urea.  He  was 
immediately  put  upon  a  moderate  antidiabetic  diet  and  returned 
to  his  home  in  Nebraska.  I  heard  from  time  to  time  for  several 
years  that  he  enjoyed  good  health  and  had  little  or  no  glycosuria 
unless  he  committed  serious  indiscretions  in  diet.  He  died  of 
"  inflammation  of  the  bowels,"  after  a  short  illness,  in  August, 
1881,  nearly  twelve  years  after  I  first  saw  him  in  1869. 

Case  N. — On  November  6,  1879  I  saw  in  consultation  a  lady 
about  fifty-eight  years  of  age,  rather  spare  in  figure,  who  had  been 
suffering  for  some  months  from  diabetes.  At  this  time  the  quantity 
of  urine  was  not  notably  increased,  the  specific  gravity  was  1030 
and  it  contained  a  small  quantity  of  sugar.  The  treatment  had  con- 
sisted mainly  of  an  imperfect  antidiabetic  diet.  A  more  rigid 
diet  was  recommended  but  it  was  not  strictly  enforced.  On  No- 
A^ember  10  and  15,  1877  the  urine  contained  a  trace  of  sugar.  On 
November  29,  1877  the  urine  was  free  from  sugar  and  the  patient 
was  much  improved.  She  left  for  her  home  in  Cuba,  and  I  saw 
her  again  on  September  2.  1880,  when  the  urine  was  still  free  from 
sugar.  In  July,  1881  she  was  passing  large  quantities  of  sugar, 
and  I  learned  that  for  several  months  the  diet  had  been  unre- 
stricted and  she  had  eaten  sweets  and  fruits  immoderately.  She 
returned  to  the  antidiabetic  diet  and  I  found  the  urine  free  from 
sugar,  with  all  the  diabetic  symptoms  relieved,  on  August  2.  1881. 
She  then  returned  to  her  former  habits  of  eating  and  the  urine  was 
found  loaded  with  sugar  on  September  27  and  October  29,  1881. 

*  This  patient  died  of  apoplexy,  June  i,  1SS4. 
23 


346        TREATMENT    OF    DIABETES    MELLITUS 

I  learned  that  she  died  "  of  diabetes,"  never  having  returned  to 
the  antidiabetic  diet,  in  Cuba,  in  1882.  During  the  last  few 
weeks  of  her  life  she  was  much  prostrated,  suffering  intensely 
from  boils  and  carbuncles,  which  were  probably  the  immediate 
cause  of  death. 

The  diet-table  which  follows  is  adapted  to  those  who 
are  able  to  provide  themselves  with  any  kind  of  food  re- 
quired, without  regard  to  cost,  rather  than  to  persons  of 
restricted  pecuniary  resources;  but  I  have  recoi^nized  the 
fact  that  those  who  are  subjected  to  an  antidiabetic  diet 
should  secure  every  possible  variety  of  food.  In  making 
this  table  I  have  drawn  largely  from  those  already  pub- 
lished, particularly  the  list  of  permissible  articles  given  by 
Bouchardat;  but  after  many  trials  of  the  so-called  anti- 
diabetic fiours  and  bread,  I  have  come  to  the  conclusion 
as  I  have  already  stated,  that  they  are  nearly  all  unreliable. 
I  prefer  to  make  patients  abstain  entirely  from  bread  or  I 
allow  the  crust  of  half  a  French  roll  two  or  three  times  daily 
if  I  can  not  eliminate  bread  altogether  from  the  diet.  The 
so-called  gluten  breads  are  not  only  unreliable  but  they 
soon  become  very  distasteful.  Wheii  ordinary  bread  is  al- 
lowed, the  physician  knows,  at  least,  about  how  much 
starch  is  taken. 

DIET-TABLE 

Breakfast. — Oysters  stewed,  without  milk  or  flour; 
clams  stewed,  without  milk  or  flour. 

Beefsteak;  beefsteak  with  fried  onions;  broiled  chicken; 
mutton  or  lamb  chops,  kidneys,  broiled,  stewed,  or  deviled; 
tripe,  pig's  feet,  game,  ham,  bacon,  deviled  turkey  or 
chicken,  sausage,  corned-beef  hash  without  potato,  minced 
beef,  turkey,  chicken  or  game,  with  poached  eggs. 

All  kinds  of  fish,  fish-roe,  fish-balls,  without  potato. 

Eggs  cooked  in  any  way  except  with  flour  or  sugar, 
scrambled  eggs  with  chipped  smoked  beef,  picked  salt  cod- 
fish with  eggs,  omelets  plain  or  with  ham,  with  smoked 
beef,  kidneys,  asparagus-points,  fine  herbs,  parsley,  truffles 
or  mushrooms. 

Radishes,  cuciunbers,  water-cresses,  butter,  pot-cheese. 

Tea  or  coffee,  with  a  little  cream  and  no  sugar.  (Glyc- 
erin may  be  used  instead  of  sugar  if  desired.) 

Light  red  wine  for  those  who  are  in  the  habit  of  taking 
wine  at  breakfast. 


TREATMENT    OF    DIABETES    MELLITUS        347 

Lunch  or  Tea. — Oysters  or  clams,  cooked  in  any 
way  except  with  flour  or  milk;  chicken,  lobster  or  any 
kind  of  salad  except  potato;  fish  of  all  kinds,  chops, 
steak,  ham,  tongue,  eggs,  crabs  or  any  kind  of  meat; 
head-cheese. 

Red  wine,  dry  sherry  or  Bass's  ale. 

Dinner. — Raw  oysters,  raw  clams. 

Soups. — Consomme  of  beef,  veal,  chicken  or  turtle; 
consomme  with  asparagus-points;  consomme  with  okra; 
ox-tail,  turtle,  terrapin;  oyster  or  clam,  without  flour  or 
milk;  chow'der,  without  milk  or  potatoes;  mock  turtle, 
mullagatawny,  tomato,  gumbo  filet. 

Fish,  etc. — All  kinds  of  fish,  lobsters,  oysters,  clams, 
terrapin,  shrimps,  crawfish,  hard-shell  crabs,  soft-shell  crabs. 
(Xo  sauces  containing  flour  or  milk.) 

Relishes. — Pickles,  radishes,  celery,  sardines,  ancho- 
vies, olives. 

Meats. — All  kinds  of  meat  cooked  in  any  way  except 
with  flour;  all  kinds  of  poultry  without  dressings  contain- 
ing bread  or  flour;  calf's  head,  kidneys,  sweet-breads,  lamb- 
fries,  ham,  tongue,  all  kinds  of  game;  veal,  fowl,  sweet- 
breads, etc.,  with  currie  but  not  thickened  with  flour.  (No 
liver.) 

Vegetables. — Truffles,  lettuce,  romaine,  chiccory,  en- 
dive, cucumbers,  spinach,  sorrel,  beet-tops,  cauliflower, 
cabbage,  Brussels-sprouts,  dandelions,  tomatoes,  radishes, 
oyster-plant,  celery,  onions,  string-beans,  water-cresses, 
asparagus,  artichauts,  Jerusalem  artichokes,  parsley,  mush- 
rooms, all  kinds  of  herbs. 

Substitutes  for  Sweets. — Peaches  preserved  in  bran- 
dy without  sugar;  wine-jelly  without  sugar;  ''  gelee  au 
kirsch  "  without  sugar;  "omelette  au  rhum  "  without  su- 
gar; "  omelette  a  la  vanille  "  without  sugar;  "  gelee  au 
rhum  "  without  sugar;  **  gelee  au  cafe  "  without  sugar. 

Miscellaneous. — Butter,  cheese  of  all  kinds,  eggs 
cooked  in  all  ways  except  with  flour  or  sugar,  sauces  with- 
out sugar,  milk  or  flour. 

Almonds,  hazel-nuts,  walnuts,  cocoanuts. 

Tea  or  coffee  with  a  little  cream  and  without  sugar. 
(Glycerin  may  be  used  instead  of  sugar  if  desired.) 

Moderately  palatable  ice-creams  and  wine  jellies  may  be 
made,  sweetened  with  pure  glycerin;  but  although  these 


348        TREATMENT   OF    DIABETES    MELLITUS 

may  be  quite  satisfactory  for  a  time  they  soon  become  dis- 
tasteful. 

Alcoholic  Beverages. — Claret,  burgundy,  dry  sher- 
ry, Bass's  ale  or  bitter  beer.     (No  sweet  wines.) 

PROHIBITED 

Ordinary  bread,  cake,  etc.,  made  with  flour;  sugar;  des- 
serts made  with  flour  or  sugar;  vegetables,  except  those 
mentioned  above;  sweet  fruits. 

ADDENDUM 

This  diet-table  is  to  be  found  only  in  my  little  book,  "  Chemical 
Examination  of  the  Urine  in  Disease."  As  it  may  possibly  be 
copied  and  used  as  it  appears  here,  I  venture  to  add  this  note, 
indicating  the  few  changes  I  have  made  since  1884: 

I  now  exclude  celery  from  the  list  of  salads  and  permit  the 
meat  of  the  claws  only  of  lobsters. 

I  no  longer  recommend  glycerin  alone  as  a  substitute  for 
sugar,  but  give  the  following  formula : 

Saccharin  (300  strength) 3  j  I 

Glycerin  (C.  P.) Oj. 

Heat   gently  to   complete    solution. 

Half  a  teaspoonful  of  this  preparation,  mixed  with  a  little 
cream,  may  be  taken  in  a  large  cup  of  coffee ;  two  teaspoonfuls 
will  sweeten  eight  ounces  of  lemonade ;  it  may  be  used  in  any 
other  way  as  a  substitute  for  sugar. 

The  ordinary  saccharin  pellets  after  a  time  become  distasteful, 
as  they  have  a  slightly  acrid  impression  and  soon  cease  to  deceive 
the  palate.  I  have  had  patients  use  the  mixture  of  saccharin  and 
glycerin  constantly  for  years  with  entire  satisfaction  and  with 
no  disturbance  of  digestion.     (November,  1902.) 


XVI 

FOUR  SELECTED  TYPICAL  CASES  OF  DIA- 
BETES MELLITUS  NOT  BEFORE  RE- 
PORTED * 

Published  in  the  "  New  York  Medical  Journal  "  for  November  22,  1884. 

In  May,  1884  I  reported  fifty  cases  of  diabetes  mellitus 
to  the  "  Section  on  Practice  of  Medicine  and  Materia  Medi- 
ca  of  the  American  Medical  Association,"  and  to  this  re- 
port, which  is  contained  in  the  "  Journal  of  the  American 
Medical  Association."  July  12,  1884,  I  refer  the  Fellows  of 
this  Association  for  full  details  of  the  treatment  employed. 
Since  this  publication  I  have  had  under  treatment  four 
cases  of  diabetes,  which  are  typical  in  many  of  their  char- 
acters, illustrating  different  conditions  of  the  disease  and 
the  effects  of  treatment  in  patients  of  dift'erent  ages. 

The  first  case,  which,  for  my  own  convenience,  I  shall 
designate  as  Case  LIII,  illustrates  the  difficulties  met  with 
in  treatment  when  the  disease  has  been  allowed  to  run  its 
course  without  restraint  for  a  number  of  months. 

Case  LIII. — The  patient  was  an  unmarried  woman,  twenty- 
two  years  of  age,  rather  slight  in  figure  when  in  health,  and  of 
medium  height.  Her  parents  are  living  and  in  perfect  health. 
The  family  history  failed  to  show  any  hereditary  tendency  to  this 
or  to  any  other  disease.  When  in  health  the  patient  weighed  140 
pounds.  This  was  the  weight  about  three  years  before  she  came 
under  my  observation.  So  far  as  I  can  judge  from  the  history 
of  the  case,  the  disease  must  have  existed  for  two  years  or  perhaps 
longer.  In  January,  1884  the  patient  had  lost  about  twenty  pounds 
in  weight,  had  excessive  urination,  an  abnormally  great  appetite 
and  thirst  and  suffered  from  a  feeling  of  exhaustion  after  moderate 
exercise.  At  that  time  she  passed,  as  was  stated,  six  to  eight 
quarts  of  urine  in  the  day,  which  was  loaded  with  sugar.  Before 
the  diabetes  had  become  developed,  she  had  enjoyed  perfect  health 
with  the  exception  of  dysmenorrhoea,  which  had  existed  since  the 

*  Read  before  the  New  York  State  Medical  Association,  November  20,  1884. 

349 


350  FOUR   CASES   OF   DIABETES 

age  of  eighteen.  She  began  to  menstruate  at  the  age  of  thirteen, 
and  at  the  age  of  eighteen  fell  from  a  wagon,  striking  on  her  feet 
and  sustaining  no  apparent  injury  at  the  time.  Since  this  fall, 
however,  she  had  persistent  dysmenorrhoea,  suffering  intense  pain 
for  six  or  eight  hours  at  every  period.  She  has  not  menstruated 
since  February,  1884;  and  in  January  and  February,  1884,  she 
suffered  no  pain.  She  was  examined  in  October,  1884,  by  Dr.  James 
B.  Hunter,  who  found  retroversion  but  advised  no  interference 
unless  menstruation  should  return. 

When  the  patient  consulted  me  on  August  25,  1884,  she  pre- 
sented all  the  characteristic  general  symptoms  of  diabetes  mellitus, 
including  excessive  appetite  and  thirst,  weariness  after  slight  ex- 
ercise, some  pruritus  vulvjc  and  an  increased  quantity  of  urine. 
Her  weight  was  92  pounds.  During  the  winter  of  1883-84  and 
the  summer  of  1884  she  had  indulged  excessively  in  starchy  mat- 
ters and  sweets,  and  since  January  had  taken  various  remedies 
without  experiencing  any  benefit. 

August  26,  1884. — The  urine  of  the  twenty-four  hours  measured 
152  fluidounces,  was  pale,  of  a  sweetish  odor  and  had  a  specific 
gravity  of  1037.  It  contained  28  grains  of  sugar  to  the  fluidounce, 
giving  a  discharge  of  4,256  grains  (8  ounces,  416  grains)  in  the 
twenty-four  hours.  There  was  no  albumin.  Microscopical  exam- 
ination revealed  the  presence  of  a  few  octahedra  of  oxalate  of  lime 
with  some  vaginal  epithelium.  She  was  at  once  put  upon  a  strict 
antidiabetic  diet,  all  starch  and  sugar  being  rigidly  excluded,  and 
was  ordered  to  take  three  drops  of  Clemens'  solution  of  bromide 
of  arsenic  three  times  daily. 

September  i. — The  quantity  of  urine  was  reduced  to  112  fluid- 
ounces.  The  sugar  was  reduced  to  12^  grains  to  the  ounce,  or 
1,400  grains  in  the  twenty-four  hours.  The  excessive  appetite 
and  thirst  and  the  pruritus  vulvae  had  disappeared.  The  dose  of 
the  Clemens'  solution  was  increased  to  five  drops.  She  felt  better 
and  stronger,  and  the  weight,  taken  September  3,  was  increased 
to  99  pounds. 

September  10. — The  weight  had  increased  to  103  pounds,  and 
the  quantity  of  urine  was  reduced  to  96  fluidounces,  with  a  specific 
gravity  of  1023.5.  The  total  discharge  of  sugar  for  the  day  was 
1,152  grains.  The  urine,  however,  presented  a  trace  of  albumin. 
The  treatment  was  continued,  with  the  addition  of  two  grains  of 
quinine  three  times  daily.  She  had  slight  uterine  pains  on  Septem- 
ber 8,  9,  and  10,  this  being  the  time  in  the  month  when  her 
periods  occurred,  but  there  was  no  menstruation.  There  was  no 
unusual  thirst  and  the  appetite  was  normal.  She  bore  the  strict 
antidiabetic  diet  very  well. 

September  24. — The  weight  had  slightly  decreased,  being  re- 
duced to  loi  pounds.  The  quantity  of  urine  was  80  fluidounces, 
with  a  specific  gravity  of  1025  and  containing  in  all  800  grains 
of  sugar.  Since  September  10  she  had  been  losing  strength  as 
well  as  weight.  The  treatment  was  continued,  with  the  addition 
of  one-quarter  of  a  pint  of  cream  and  a  tablespoonful  of  whisky 
twice  daily. 


FOUR   CASES    OF    DIABETES  351 

October  10. — The  weight  was  reduced  to  96  pounds.  The  quan- 
tity of  urine  was  80  fluidounces,  with  a  specific  gravity  of  1023 
and  containing  in  all  720  grains  of  sugar.  The  patient  had  fol- 
lowed the  treatment,  dietetic  and  medicinal,  most  faithfully.  She  had 
taken,  for  about  four  weeks,  griddlecakes  made  of  Hecker's  farina, 
which  contains  only  one  or  two  per  cent,  of  starch (?).  Notwith- 
standing the  rigid  diet,  however,  I  had  been  unable  to  reduce  the 
quantity  of  sugar  below  9  or  10  grains  to  the  fluidounce  of  urine, 
or  700  to  800  grains  in  the  twenty-four  hours,  and  the  strength 
and  general  health  showed  no  improvement  since  September  24. 
I  decided  to  try  to  arrest  the  discharge  of  sugar  by  an  absolute 
fast  of  twenty-eight  hours — a  method  recommended  by  Cantani. 
To  this  plan  the  patient  cheerfully  assented.  She  accordingly 
fasted  from  8  a.m.,  October  10,  to  12  m.,  October  11,  remaining 
in  bed  most  of  the  time  and  taking  nothing  but  water.  The  urine 
passed  at  the  close  of  the  fast  contained  two  grains  of  sugar  to  the 
fluidounce ;  but  it  presented  oxalate  of  lime,  a  small  quantity  of 
albumin  and  a  few  small  granular  casts.  She  bore  the  fast  very 
well,  had  a  good  appetite  the  next  day  and  for  several  days  felt 
better  than  she  had  for  weeks.  Following  the  fast  the  former 
treatment  was  resumed. 

October  15. — The  quantity  of  urine  was  somewhat  reduced.  Its 
specific  gravity  was  1030  and  it  contained  9  grains  of  sugar  to 
the  fluidounce.  There  was  still  a  little  albumin  with  a  few  granular 
casts.  The  patient  left  for  her  home  in  Georgia  on  the  following 
■day.  She  was  in  much  better  general  health  than  when  I  first  saw 
her  on  August  25,  but  I  had  found  it  impossible  to  arrest  the  dis- 
charge of  sugar. 

My  prognosis  in  this  case  is  not  entirely  favorable.  It 
is  probable  that  the  excessive  indulgence  in  sweets  and  in 
starchy  articles  of  food  for  several  months  dtiring  the  height 
of  the  disease  has  rendered  the  glycosuria  uncontrollable 
beyond  a  certain  point.  Her  present  safety  undoubtedly 
lies  in  an  antidiabetic  diet,  and  a  return  to  sweets  and 
starch  would  probably  be  promptly  followed  by  a  return  of 
all  of  the  grave  symptoms  of  the  disease.* 

The  following  case  is  in  striking  contrast  to  the  one 
just  recited: 

Case  LV. — The  patient  v.'as  a  young  girl,  of  medium  height 
and  development,  fifteen  years  of  age.  Her  father  and  mother  are 
living  and  in  good  health  and  there  is  no  hereditary  tendency  to 
disease.  A  sister  of  the  patient  died  at  the  age  of  nineteen,  prob- 
ably of  diabetes  mellitus.     The  patient  began  to  menstruate  at  the 

*  I  received  a  letter  from  the  father  of  this  patient,  dated  November  2, 
1884,  stating  that  "  she  arrived  safely  without  detention,  and  bore  the  fatigue 
of  the  trip  astonishingly  well.  She  is,  I  think,  evidently  stronger  and  better 
than  when  she  first  placed  herself  under  your  treatment." 


352  FOUR   CASES    OF    DIABETES 

age  of  thirteen  and  has  menstruated  regularly  since  that  time. 
She  was  in  perfect  health  up  to  January,  1884,  when  she  began 
to  lose  flesh  slightly  and  was  "  ailing  "  for  a  few  weeks.  She  soon 
improved  in  general  health  and  was  apparently  well  until  the  mid- 
dle of  August,  1884,  when  she  was  found  to  be  passing  about  two 
quarts  of  urine  daily,  the  specific  gravity  of  which  was  said  to 
be  1052.  Since  that  time  she  has  been  on  a  moderately  restricted 
diet  and  has  taken  various  remedies.  She  suffered  somewhat  from 
thirst  during  August  and  September.  Her  urine  was  found  some- 
times to  contain  a  little  sugar  and  sometimes  was  free  from  sugar. 

October  8,  1884. — I  made  a  thorough  physical  examination  of 
the  patient  and  found  no  disease.  The  urine  was  rather  less  in 
quantity  than  normal,  had  a  specific  gravity  of  1031  and  contained 
no  sugar.  The  only  abnormal  condition  of  the  urine  was  the  pres- 
ence of  a  large  number  of  octahedra  of  oxalate  of  lime.  The  diet 
had  been  moderately  restricted.  I  ordered  that  the  diet  be  unre- 
stricted for  twenty-four  hours. 

October  10. — After  twenty-four  hours  of  unrestricted  diet,  the 
quantity  of  urine  was  slightly  increased.  It  had  a  specific  gravity 
of  1036.5  and  contained  31  grains  of  sugar  to  the  fluidounce. 
There  were  none  of  the  characteristic  general  symptoms  of  dia- 
betes. I  ordered  a  strict  antidiabetic  diet,  three  drops  of  Clemens' 
solution  of  bromide  of  arsenic  three  times  daily,  the  dose  to  be 
graduallv  increased  to  five  drops,  and  a  pill  of  one-quarter  of  a 
grain  of  codein  and  one-twelfth  of  a  grain  of  podophyllin  at  night, 
to  relieve  constipation  should  it  be  troublesome.  The  patient  then 
left  for  her  home  in  Virginia. 

October  16. — I  heard  from  this  patient  and  received  a  specimen 
of  urine.  The  treatment  had  been  followed  strictly.  She  had  felt 
perfectly  well  since  her  return  to  Virginia  and  was  passing  urine 
in  normal  quantity.  The  urine  had  a  specific  gravity  of  1015  and 
contained  no  su""Hr. 

In  this  case  the  glycosuria  seemed  to  be  easily  control- 
lable. After  examining  the  urine  I  wrote  to  the  friends 
as  follows: 

"  I  suggest  that  the  dietetic  and  other  measures  of  treatment 
be  strictly  followed  until  the  middle  of  December.  If.  at  the  end 
of  that  time,  the  urine  should  continue  free  from  sugar,  the  patient 
may  begin  to  eat  a  little  bread  and  gradually  return  to  the  usual 
diet,  except  that  she  should  never  eat  sugar  or  sweets.  The  urine 
should  be  examined  from  time  to  time  while  she  is  in  process  of 
returning  to  the  normal  diet." 

My  prognosis  in  this  case  is  favorable.  With  proper 
attention  to  the  diet  I  should  expect  a  cure;  but  it  will  be 
necessary  to  examine  the  urine  occasionally  for  a  long  time 
in  order  to  detect,  at  the  earliest  moment,  any  tendency  to- 
a  return  of  the  glycosuria. 


FOUR   CASES    OF    DIABETES  353 

Case  LI. — This  patient  was  a  robust  man,  unmarried,  thirty- 
four  years  of  age,  5  feet  7  inches  in  height  and  weighed  177 
pounds.  He  had  always  eaten  largely  of  bread  and  sweets.  For 
several  weeks  he  had  a  moderate  increase  in  thirst  and  had  not 
been  "  feeling  very  well."  His  urine  had  been  examined  and  it 
was  said  to  contain  sugar.  His  previous  health  had  been  good. 
He  had  occasionally  committed  sexual  excesses. 

I  examined  this  patient  on  April  8,  1884  and  found  no  disease. 
The  urine  was  somewhat  less  in  quantity  than  normal,  with  a  spe- 
cific gravity  of  1035  and  was  turbid  with  urates.  It  contained  no 
sugar.  During  the  day  on  which  this  urine  was  passed  the  patient 
had  abstained  from  bread  and  sweets. 

April  10,  1884. — I  examined  a  specimen  of  the  urine  passed  dur- 
ing the  day,  the  diet  having  been  unrestricted.  It  had  a  specific 
gravity  of  1026  and  contained  a  small  quantity  of  sugar. 

June  2. — Since  April  10  the  patient  had  followed  a  strict  anti- 
diabetic diet  and  had  taken  three  drops  of  Clemens'  solution  of 
bromide  of  arsenic  three  times  daily.  His  urine  had  a  specific  grav- 
ity of  1030,  was  normal  in  quantity  and  contained  no  sugar.  The 
patient  felt  perfectly  well,  but  his  weight  had  been  reduced  to  167 
pounds.  The  dose  of  Clemens'  solution  was  increased  to  five 
drops. 

July  16. — The  patient  was  still  perfectly  well,  the  diet  was  not 
irksome  and  the  urine  was  normal,  free  from  sugar  and  had  a 
specific  gravity  of  1024.  The  weight  had  been  reduced  to  161 
pounds.    The  treatment  was  continued. 

August  I. — The  patient  continued  well,  but  the  weight  was  re- 
duced to  159  pounds.  The  urine  was  normal,  free  from  sugar  and 
had  a  specific  gravity  of  1029.     The  treatment  was  continued. 

August  14. — The  patient  continued  well  and  the  weight  had 
increased  to  161  pounds.  The  urine  contained  no  sugar  and  had 
a  specific  gravity  of  1026. 

August  20. — The  patient  continued  in  the  same  condition.  The 
weight  was  157  pounds  and  he  looked  and  felt  in  perfect  health. 
The  urine  contained  no  sugar  and  had  a  specific  gravity  of  1031. 
The  patient  then  passed  from  under  my  observation.  The  Clemens' 
solution  was  stopped  and  he  was  instructed  to  gradually  return  to 
a  normal  diet,  but  never  to  eat  sugar  or  sweets  and  to  carefully 
abstain  from  excesses  of  any  kind. 

In  this  case  the  glycosuria  was  readily  controllable  and 
an  apparent  cure  was  effected. 

The  fourth  case  is  that  of  a  man,  fifty-nine  years  of  age, 
in  whom  the  disease,  although  of  at  least  a  year's  standing, 
yielded  promptly  to  treatment. 

Case  LII. — The  patient,  a  married  man,  fifty-nine  years  of  age, 
was  5  feet  8j  inches  in  height  and  weighed  227  pounds.  He  was 
robust,  had  always  enjoyed  good  health  and  had  been  rather  a  free 
liver,  but  without  excesses  of  any  kind.  The  family  history  gave 
no  evidence  of  hereditary  tendency  to  disease.    For  the  nine  months 


354  FOUR    CASES    OF    DIABETES 

previous  to  the  time  when  he  came  under  my  observation  he  had 
suffered  from  excessive  urination,  annoying  thirst,  abnormal  weari- 
ness and  impairment  of  appetite.  During  this  period  he  had  lost 
about  twenty  pounds  in  weight. 

August  II,  1884. — I  examined  a  specimen  of  the  urine.  Its 
quantity  in  twenty-four  hours  had  not  been  measured  but  was 
undoubtedly  excessive.  It  had  a  specific  gravity  of  1023  and  con- 
tained considerable  sugar  with  abundant  uric  acid  crystals.  He 
was  at  once  put  upon  a  rigid  antidiabetic  diet,  with  three  drops 
of  Clemens'  solution  of  bromide  of  arsenic  three  times  daily. 

August  19. — The  general  diabetic  symptoms  had  entirely  disap- 
peared. The  urine  was  normal,  with  a  specific  gravity  of  1020 
and  free  from  sugar.    The  weight  was  unchanged  at  227  pounds. 

August  26. — The  patient  felt  perfectly  well.  The  urine  had  a 
specific  gravity  of  1012.5  and  was  free  from  sugar.  The  dose  of 
Clemens'  solution  was  increased  to  five  drops. 

September  28. — The  patient  continued  to  feel  perfectly  well. 
The  urine  had  a  specific  gravity  of  1030  and  was  free  from  sugar. 
The  weight  had  increased  to  235  pounds.  The  Clemens'  solution 
was  stopped  and  the  patient  was  allowed  to  eat  a  little  bread. 

October  11. — The  patient  felt  that  he  was  entirely  cured.  His 
weight  was  233  pounds.  The  urine  was  perfectly  normal,  had  a 
specific  gravity  of  1020  and  was  free  from  sugar.  He  was  directed 
to  follow  a  reasonable  diet,  not  abstaining  entirely  from  starchy 
matters,  but  avoiding  sugar  and  sweets.  He  was  directed  to  have 
his  urine  examined  again  in  about  six  weeks. 

The  limited  time  at  my  disposal  prevents  me  from  giv- 
ing the  diet-table  for  diabetics  and  other  details  of  treat- 
ment, which  would  be  merely  a  repetition  of  what  is  con- 
tained in  my  paper  on  the  ''  Treatment  of  Diabetes  Mel- 
litus,"  published  in  the  "  Journal  of  the  American  Medical 
Association,"  July  12,  1884,  and  in  the  sixth  edition  of  my 
little  book  on  the  "  Chemical  Examination  of  the  Urine  in 
Disease."  The  diet-table  is  very  varied  and  is  not  difificult 
to  follow,  the  greatest  hardship  to  patients  being  depriva- 
tion of  bread.  It  is  a  curious  fact,  however,  that  after  fol- 
lowing a  strict  diet  for  two  or  three  weeks,  diabetics  lose 
their  craving  for  many  prohibited  articles  of  food,  and  the 
diet  becomes  by  no  means  irksome.  The  patients,  in  all 
of  the  cases  here  reported,  were  in  good  circumstances  and 
both  willing  and  able  to  follow  strictly  the  prescribed  diet. 

In  presenting  an  account  of  these  four  typical  cases  to 
the  Association,  I  have  purposely  put  the  unfavorable  case 
first.  This  is  the  second  case  that  I  have  met  with  in  which, 
patients  being  willing  to  submit  absolutely  to  treatment, 
I  have  not  been  able  to  arrest  the  glycosuria.     In  this  case, 


FOUR   CASES    OF    DIABETES  355 

for  many  months  the  patient  indulged  inordinately  in 
sweets;  and  the  disease,  which  was  complicated  with  albu- 
minuria, had  become  so  thoroughly  confirmed  that  al- 
though the  general  symptoms  were  controlled,  even  total 
abstinence  from  food  did  not  remove  the  sugar  from  the 
urine  after  the  first  week  of  treatment. 


XVII 

LITHIUM  CARBONATE  AND  SODIUM  AR- 
SENATE DISSOLVED  IN  CARBONIC  ACID 
WATER  IN  THE  TREATMENT  OF  DIABETES 
MELLITUS 

Published  in  "  The  Medical  News  "  for  July  9,  1887. 

At  a  recent  meeting  of  the  Therapeutical  Society  of 
Paris,  Dr.  Martineau  made  a  brief  communication  in  which 
he  stated  that  for  several  years  he  had  treated  cases  of  dia- 
betes mellitus  with  a  solution  of  lithium  carbonate  and 
sodium  arsenate  in  ordinary  carbonic  acid  water,  to  the  ex- 
clusion of  every  other  medicinal  remedy  and  with  a  moder- 
ately strict  antidiabetic  diet.  Dr.  Martineau  claimed  that 
he  had  cured  sixty-seven  out  of  seventy  cases  of  arthritic 
diabetes  by  this  method  of  treatment,  which  he  had  bor- 
rowed from  a  practitioner  now  dead,  the  late  Prof.  Rouget^ 
of  Paris.  The  communication  was  discussed  by  Dr.  Du- 
jardin-Beaumetz  and  others,  who  regarded  the  method  as 
so  simple  and.  to  say  the  least,  innocuous,  that  it  was  worthy 
of  trial. 

The  preparation  recommended  by  Dr.  Martineau  was 
the  following.*  Into  an  apparatus  such  as  is  commonly 
used  in  Paris  for  making  carbonic  acid  water,  are  put  twenty 
centigrammes  of  lithium  carbonate  and  a  tablespoonful  of 
a  solution  of  twenty  centigrammes  of  sodium  arsenate  in 
five  hundred  grammes  of  distilled  water.     The  quantity  of 

*  "  Bulletin  et  memoires  de  la  societe  de  therapeutique,"  Paris,  30  mars, 
1887,  i8e  annee,  No.  6,  p.  41. 

Reduced  to  the  English  standard  the  formula  would  be  about  as  follows  : 

Lithium  carbonate   3  grains. 

Sodium  arsenate    iVi  grain. 

Carbonic  acid  water 2  pints. 

This  formula  has  been  published  in  a  number  of  medical  journals.  In  some  it 
is  stated  that  a  teaspoonful  of  the  solution  of  sodium  arsenate  is  used  instead  of  a 
tablespoonful.  This  error  arises  from  a  faulty  translation  of  "  cuilleree  a  bouche," 
which  means  a  tablespoonful.     The  term  for  a  teaspoonful  is  "  cuilleree  k  cafe.'* 

356 


MEDICINAL   TREATMENT    OF    DIABETES        357 

carbonic  acid  water  used  is  about  one  litre.  This  quantity 
is  to  be  drunk  by  the  patient  during  each  day,  either  by 
itself  or  mixed  with  ordinary  wine  at  meals. 

The  simplicity  of  the  proposed  remedy  led  me  to  make 
an  efifort  to  test  its  efificacy  in  certain  obstinate  cases  under 
treatment  for  diabetes.  I  endeavored  first  to  have  the 
agents  introduced  into  the  ordinary  siphons  of  soda  water 
prepared  and  sold  in  New^  York;  but  the  manufacturers 
were  unwilling  to  do  this  and  I  was  forced  to  adopt  some 
other  method  of  preparation.  It  was  finally  suggested  to 
me  to  put  up  the  preparation  in  ordinary  beer  bottles  with 
patent  stoppers  which  could  be  replaced  after  using  a  cer- 
tain quantity.  This  was  done,  two  of  these  bottles  making 
the  equivalent  of  the  quantity  administered  daily  by  Dr. 
Martineau. 

I  was  not  prepared  to  make  a  trial  of  the  remedy  before 
the  middle  of  April  and  have  used  it  since  then  in  but 
three  cases — a  time  too  short,  and  a  number  of  cases  too 
small  to  admit  of  anything  like  definite  conclusions.  How- 
ever, in  the  hope  of  inducing  others  to  make  similar  trials.  I 
venture  to  present  the  imperfect  results  of  my  own  brief 
experience.* 

Case  LXXXV. — x\n  unmarried  lady,  fifty  years  of  age,  weigh- 
ing 115  pounds.  Her  weight  in  health  was  140  pounds.  The 
disease  was  recognized  six  months  before  she  came  under  my 
care. 

March  11,  1886. — The  general  diabetic  symptoms  were  marked, 
and  the  virine  contained  2i  grains  of  sugar  per  ounce.  The  patient 
was  put  on  an  antidiabetic  diet,  according  to  my  published  diet- 
table,f  with  Clemens'  solution  of  bromide  of  arsenic,  five  drops 
three  times  daily.  March  19  the  quantity  of  sugar  was  7  grains 
per  ounce;  March  26,  14  grains;  April  2  there  was  no  sugar;  and 
April  7  no  sugar.  From  March  26  to  April  7  the  diet  was  abso- 
lutely antidiabetic,  no  bread  being  taken. 

June  17. — The  urine  had  been  free  from  sugar  since  April  2 
under  the  antidiabetic  diet.  The  quantity  was  normal  and  the 
body-weight  had  increased  by  four  pounds.  The  patient  expressed 
herself  as  feeling  "  nearly  well." 

July  28. — The  diet  for  several  weeks  had  been  very  imperfect, 
the  diabetic  symptoms  had  returned,  and  the  urine  contained  24 

*  The  numbers  of  these  cases  are  made  to  correspond  with  the  numbers  in 
my  book  of  records. 

+  "  Jorunal  of  the  American  Medical  Association,"  July  12,  1SS4,  and 
"  Manual  of  Chemical  Examination  of  the  Urine  in  Disease,"  sixth  edition. 
New  York,  1884,  p.  85.     See  also  p.  346  of  this  volume. 


358       MEDICINAL   TREATMENT   OF    DIABETES 

grains  of  sugar  per  ounce.  From  this  date  until  April  15,  1887^ 
sugar  was  found  in  the  urine  at  every  examination,  the  quantity 
apparently  varying  with  the  diet.  During  this  time  I  made  ten 
examinations.  The  general  diabetic  symptoms  were  much  dimin- 
ished in  prominence  although  they  were  distinct.  The  body-weight 
did  not  undergo  much  change. 

April  15,  1887. — The  daily  quantity  of  urine  was  45  ounces 
containing  20i  grains  of  sugar  per  ounce. 

April  16. — With  no  change  in  general  treatment,  the  patient 
was  put  on  the  solution  of  lithia  and  arsenic,  about  two  pints 
daily. 

April  26. — The  quantity  of  urine  was  37  ounces  containing  8 
grains  of  sugar  per  ounce. 

May  4. — The  diet  had  been  relaxed.  The  quantity  of  urine  was 
52  ounces  containing  18  grains  of  sugar  per  ounce. 

May  12. — The  diet  had  been  more  rigid.  The  quantity  of  urine 
was  32  ounces  containing  6  grains  of  sugar  per  ounce. 

May  29. — The  diet  had  been  imperfect.  The  quantity  of  urine 
was  about  40  ounces  containing  244  grains  of  sugar  per  ounce. 

On  May  12  there  was  some  swelling  of  the  eyelids  and  the 
quantity  of  the  solution  of  lithia  and  arsenic  was  reduced  one-half. 
On  May  14,  15  and  16  the  lithia  and  arsenic  were  omitted. 

The  patient  was  weak  and  depressed  when  the  treatment  with 
lithia  and  arsenic  was  begun.  On  May  23,  about  five  weeks  after, 
she  felt  much  better  and  stronger,  with  a  gain  of  two  or  three 
pounds  in  weight. 

With  the  exception  of  the  indefinite  statement  by  the  patient 
that  she  felt  better  in  spirits  and  stronger,  the  lithia  and  arsenic 
seemed  to  have  produced  no  marked  effects.  This  patient  is  pecul- 
iarly susceptible  to  starchy  and  saccharine  articles  of  food.  Under 
measures  of  treatment  that  had  been  very  beneficial  in  other  cases, 
she  has  lately  shown  little  or  no  improvement ;  and  the  most  favor- 
able view  to  take  of  the  case  is  that  the  disease,  under  proper  die- 
tetic treatment,  may  not  progress  rapidly. 

Case  XCIII. — A  gentleman,  sixty-one  years  of  age,  5  feet  5J 
inches  tall,  weighing  157  pounds.  The  disease  was  recognized 
fourteen  years  ago. 

November  19,  1886,  the  patient  came  under  my  care.  The 
quantity  of  urine  was  90  ounces  containing  19  grains  of  sugar 
per  ounce.  The  diet  had  been  very  imperfect,  milk  and  grapes 
having  been  taken  freely.  He  was  put  upon  a  strict  antidiabetic 
diet,  with  Clemens'  solution,  five  drops  three  times  daily,  and  one 
and  a  half  ounces  of  whisky  three  times  daily.  I  saw  the  patient 
but  once  and  heard  of  the  progress  of  the  case  from  time  to  time 
from  his  physician  in  the  country. 

April  6,  1887. — The  patient  had  not  been  doing  well.  He  had 
lost  thirteen  pounds  in  weight ;  the  appetite  had  become  very  poor 
and  there  was  great  suffering  from  pains  about  the  chest  and  in 
the  limbs. 

April  20. — The  general  condition  was  about  the  same  but  the 
quantity  of  urine  was  normal  with  6j  grains  of  sugar  per  ounce. 


MEDICINAL    TREATMENT    OF    DIABETES        359 

The  patient  was  then  put  upon  the  solution  of  lithia  and  arsenic, 
two  pints  daily. 

May  II. — The  general  condition  was  about  the  same  but  the 
quantity  of  urine  was  reduced  to  40  ounces  and  it  contained  no 
sugar. 

May  19. — It  was  reported  to  me  that  the  general  condition  of 
the  patient  was  better  and  that  he  was  stronger.  No  report  was 
made  of  the  condition  of  the  urine. 

Case  XCV. — A  married  lady,  sixty-three  years  of  age,  of  me- 
dium height,  weighing  155  pounds.  At  the  present  time  she  has 
been  under  my  care  for  a  little  more  than  three  months.  The  dis- 
ease was  recognized  twelve  years  ago.  In  health  the  patient 
weighed  about  200  pounds. 

February  9,  1887. — The  general  diabetic  symptoms  are  well 
marked.  The  quantity  of  urine  is  excessive  and  it  contains  23 
grains  of  sugar  per  ounce.  The  patient  was  put  upon  the  anti- 
diabetic diet,  with  Clemens'  solution,  iive  drops  three  times  daily. 

February  14. — The  quantity  of  urine  was  normal  and  it  had  so 
continued  up  to  this  date.  The  quantity  of  sugar  was  13  grains 
per  ounce.    The  diabetic  symptoms  had  disappeared. 

April  4. — The  urine  has  been  examined  regularly  once  a  week 
and  the  quantity  of  sugar  has  been  gradually  reduced  to  one  grain 
per  ounce.  The  appetite  became  very  poor  about  a  week  ago,  and 
insomnia  was  very  troublesome,  with  shooting  pains  over  the  liver. 

April  17. — The  patient  was  put  upon  the  solution  of  lithia  and 
arsenic,  two  pints  daily. 

April  25. — The  quantity  of  urine  was  about  normal  and  it 
contained  no  sugar. 

May  17. — The  general  condition  has  improved.  Since  April 
25  the  urine  has  contained  about  one  grain  of  sugar  per  ounce. 
Within  the  past  eight  months  the  patient  has  lost  fourteen  pounds 
in  weight. 

May  24. — The  general  condition  of  the  patient  is  much  im- 
proved. The  quantity  of  urine  is  normal  and  it  contains  about 
one  grain  of  sugar  per  ounce. 

The  general  result  of  the  observations  on  the  three  cases 
reported  is  quite  indefinite.  The  effects  of  the  solution 
of  lithia  and  arsenic  were  not  well  marked,  and  the  slight 
improvement  under  its  use  in  Cases  XCIII.  and  XCV. 
might  have  beeii  due  to  other  causes.  I  shall,  however, 
contintie  the  remedy  in  these  three  cases  and  employ  it  in 
other  cases  until  I  shall  have  given  it  a  fair  trial;  btit  I  do 
not  feel  that  it  would  be  prudent  in  any  case  to  relax  the 
dietetic  treatment. 

With  other  so-called  specifics  for  diabetes  mellitus  I 
have  had  some  experience. 

I  have  given  calcium  chloride  in  a  number  of  cases,  with 
entirely  negative  results. 


36o       MEDICINAL    TREATMENT    OF    DIABETES 

In  several  cases  I  have  used  jaml)ol,  also  with  negative 
results. 

1  have  never  given  opium,  except  for  the  relief  of  pain 
and  insomnia;  but  in  cases  in  which  it  has  been  used  it  has 
been  well  tolerated. 

I  nearly  always  prescribe  at  first  Clemens'  solution  of 
bromide  of  arsenic.  This  remedy  does  no  harm,  and  in 
many  cases  it  seems  to  exert  some  control  over  the  thirst, 
polyuria  and  the  quantity  of  sugar  in  the  urine. 

I  invariably  interdict  the  use  of  milk  and  skim  milk. 
In  a  number  of  cases  in  which  it  has  been  taken  by  patients 
on  their  own  responsibility,  I  have  observed  that  it  prompt- 
ly induced  thirst,  polyuria  and  an  immense  increase  in  the 
discharge  of  sugar.  In  some  instances  in  which  my  pub- 
lished diet-table  has  been  copied,  milk  has  been  added. 
This  addition,  it  seems  to  me,  is  most  unwarrantal)le;  and 
the  use  of  milk  more  than  counteracts  the  beneficial  results 
to  be  expected  from  the  antidiabetic  diet  properly  carried 
out. 

For  the  past  three  years  I  have  recommended  a  gluten 
bread  which  at  first  contained  between  two  and  five  per 
cent,  of  starch.  Within  a  year,  however,  it  has  seemed  to 
act  unfavorably.  I  have  lately  had  a  number  of  analyses 
made  of  this  bread,  and  it  has  been  found  to  contain  about 
thirty  per  cent,  of  starch.  Within  the  last  two  months  I 
have  abandoned  its  use,  although  this  has  greatly  in- 
creased the  difficulties  of  dietetic  treatment. 

I  have  not  been  able  to  study  the  details  of  the  seventy 
cases  mentioned  by  Dr.  Martineau,  sixty-seven  of  which 
he  reported  as  cured.* 

The  experience  of  all  who  have  followed  out  any  con- 
siderable number  of  cases  of  diabetes  teaches  that  the  gly- 
cosuria nearly  always  returns  under  a  careless  diet ;  and  my 
ow'n  experience  is  no  exception  to  this  general  rule.  That 
such  an  exception  should  have  occurred  in  the  experience 
of  Dr.  Martineau  would,  indeed,  be  remarkable. 

Including  the  three  cases  already  briefly  reported,  I 
have  now  under  observation  and  treatment  ten  cases  which 
I  have  follow-ed  for  variable  periods.     It  may  be  interesting 

*  A  brief  account  of  three  cases,  treated  by  Dr.  Martineau,  is  given  in  the 
*'  Therapeutic  Gazette,"  Philadelphia,  May  i6,  1887,  p.  330. 


MEDICINAL   TREATMENT    OF    DIABETES       361 

to  compare  seven  of  these  cases  with  the  three  treated  witli 
the  solution  of  Hthia  and  arsenic. 

Case  LXXXIII. — A  gentleman,  fifty-eight  years  of  age,  5  feet 
7  inches  tall,  weighing  156  pounds.  I  began  the  treatment  of  this 
case  January  17,  1886.  The  disease  had  been  recognized  four  years 
before.  The  patient  had  been  under  the  care  of  an  eminent  English 
physician,  who  gave  the  opinion,  after  two  or  three  years  of  treat- 
ment, that  the  disease  would  never  be  entirely  cured. 

January  17,  1886. — The  diabetic  symptoms  were  distinct  but 
slight.  The  patient  had  been  under  a  moderately  strict  antidiabetic 
diet.  The  quantity  of  urine  was  60  ounces  containing  2h  grains  of 
sugar  per  ounce.  The  patient  was  put  upon  an  absolute  antidia- 
betic diet,  without  any  bread,  for  two  days,  and  Clemens'  solution, 
three  drops  three  times  daily,  the  dose  to  be  increased  in  five  days 
to  five  drops.  Two  days  after,  the  urine  was  free  from  sugar.  The 
patient  has  continued  to  be  perfectly  well  in  every  way  up  to  the 
present  time,  being  very  actively  engaged  in  business. 

From  January  17,  1886  to  May  22,  1887  the  urine  has  been 
examined  twenty-seven  times.  On  December  19,  1886  a  trace  of 
sugar  was  found,  this  being  the  only  examination  in  which  the 
urine  was  not  free  from  sugar.  The  diet  was  strict,  antidiabetic 
bread  being  used  for  the  first  three  months.  Since  then,  while  the 
patient  has  been  careful,  the  diet  has  been  rather  liberal  and  the 
patient  has  not  suffered  any  serious  privation. 

Case  LXV. — A  gentleman,  forty-one  years  of  age,  6  feet  tall, 
weighing  205  pounds.  The  disease  had  been  recognized  six  months 
and  the  patient  had  lost  about  forty  pounds  in  weight. 

April  22,  1885. — The  patient  had  the  usual  diabetic  symptoms 
in  a  marked  degree.  The  quantity  of  urine  was  excessive  and  it 
contained  21  grains  of  sugar  per  ounce.  The  patient  was  subjected 
to  essentially  the  same  course  of  treatment  as  detailed  in  Case 
LXXXIII.  In  four  days  the  urine  was  found  free  from  sugar 
and  the  diabetic  symptoms  had  disappeared.  Between  April  22 
and  December  22,  1885  ^he  virine  was  examined  thirty-one  times. 
August  ID,  the  urine  contained  9  grains  of  sugar  per  ounce;  Sep- 
tember I,  no  sugar;  December  10,  3i  grains  of  sugar  per  ounce; 
December  22,  no  sugar.  On  the  two  occasions  when  sugar  was 
found,  its  presence  was  probably  due  to  indiscretions  of  diet,  and 
it  promptly  disappeared  under  a  strict  regimen.  After  the  first 
two  months  of  treatment  the  diet  was  but  little  restricted.  Since 
December  22  I  have  seen  the  patient  casually  from  time  to  time 
and  he  has  reported  himself  as  perfectly  well. 

Case  XCI. — A  gentleman,  fifty-six  years  of  age,  5  feet  8 
inches  tall,  weighing  166  pounds.  Twelve  years  ago  he  weighed 
200  pounds.  Sugar  was  recognized  in  the  urine  eight  years  before 
the  patient  came  under  my  care. 

October  14,  1886. — The  general  diabetic  symptoms  are  slight. 
For  the  past  eight  years  the  patient  has  been  under  a  very  imper- 
fect antidiabetic  diet,  and  so  far  as  I  can  learn,  the  presence  of 
sugar  in  the  urine  has  been  constant.  The  urine  is  now  normal  in 
24 


362       MEDICINAL   TREATMENT   OF    DIABETES 

quantity  and  contains  25^  grains  of  sugar  per  ounce.  The  patient 
was  put  upon  essentially  the  same  course  of  treatment  as  in  Cases 
LXXXIII.  and  LXV.  On  October  21  the  urine  contained  13^ 
grains  of  sugar  per  ounce ;  on  October  26,  1 1  grains  per  ounce. 

October  29. — The  patient  was  subjected  to  an  absolute  fast  of 
thirty-six  hours,  after  the  method  proposed  by  Cantani,*  taking 
during  that  time  nothing  but  water.  The  fast  was  borne  very 
well,  and  on  the  day  following  the  patient  expressed  himself  as. 
"  feeling  as  well  as  he  had  felt  in  ten  years."  The  quantity  of 
urine  during  the  last  twenty-four  hours  of  the  fast  was  25  ounces 
and  it  contained  no  sugar.  The  ordinary  antidiabetic  diet  was 
then  resumed.  October  31,  the  urine  contained  13  grains  of  sugar 
per  ounce;  November  3,  10  grains.  From  November  9  to  20,  there 
was  no  sugar.  On  February  2^,  1887  I  heard  from  the  patient. 
His  urine  had  been  repeatedly  examined  and  no  sugar  had 
been  found.  He  reported  that  his  "  general  health  had  been 
very  good." 

Case  VI. — A  gentleman,  about  sixty  years  of  age,  5  feet  6 
inches  tall,  weighing  185  pounds.  From  March  22,  1878  to  Febru- 
ary 24,  1885  I  had  repeatedly  examined  the  urine  of  this  patient 
while  he  was  partly  under  the  care  of  the  late  Dr.  Austin  Flint. 
From  April  21,  1878  to  January  10,  1882  the  urine  was  free  from 
sugar.  From  October  14,  1882  to  February  24,  1885  the  urine  had 
generally  contained  sugar,  sometimes  in  large  quantity. 

December  13,  1886. — The  patient  came  under  my  direct  care. 
The  quantity  of  urine  was  about  normal  and  it  contained  18  grains 
of  sugar  per  ounce.  The  patient  was  languid  and  easily  wearied 
but  had  no  abnormal  thirst.  He  was  put  upon  the  usual  treatment 
and  took  no  bread.  On  December  19  he  was  much  improved.  The 
urine  contained  7^  grains  of  sugar  per  ounce.  The  variations  in 
sugar  for  a  few  weeks  were  as  follows :  December  23,  6  grains  per 
ounce;  December  26,  3 J  grains;  January  i,  1887,  a  trace  of  sugar; 
January  8,  a  trace  of  sugar. 

May  24,  1887. — The  patient  had  been  absent  from  the  city  from 
January  12  to  May  4.  He  now  feels  perfectly  well.  On  May  4  and 
24  the  urine  contained  a  faint  trace  of  sugar.  Since  December  13, 
1886  the  patient  has  taken  no  bread.  The  antidiabetic  diet  has 
been  rigidly  carried  out  and  the  appetite  has  been  tempted  by  skil- 
fully prepared  dishes  within  the  limits  of  the  "  diet-table,"  so  that 
the  want  of  bread  has  not  been  a  serious  privation.t 


*  Cantani,  "  Le  diabete  sucre,"  p.  402.     Paris,  1876. 

+  In  many  regards  this  case  is  of  great  interest.  Its  progress  from  March 
22,  187S  to  August  15,  1883  was  reported  in  my  article  in  the  "Journal  of  the 
American  Medical  Association  "  for  July  12,  1S84,  Case  F.  On  April  18,  1871, 
while  the  patient  was  under  the  care  of  Dr.  Brown-Sequard  for  some  slight 
nervous  disorder,  I  examined  the  urine  and  found  it  normal.  I  recognized 
sugar  in  the  urine,  March  22,  1878.  Under  a  moderately  strict  diet  the  sugar 
promptly  disappeared  and  was  not  discovered  again  until  October  14,  1882, 
three  years  and  nearly  seven  months  after,  although  the  diet  was  unrestricted 
during  the  greatest  part  of  this  time.  This  might  have  been  regarded  as  a  case 
of  transient  glycosuria  if  diabetes  had  not  become  confirmed  in  1882  and  1883, 


MEDICINAL   TREATMENT    OF    DIABETES       363 

Case  XCII. — A  gentleman,  fifty-one  years  of  age,  5  feet  11 
inches  tall,  weighing  208  pounds.  Five  months  before  he  came  un- 
der my  care  he  was  examined  for  life  insurance  and  no  sugar  was 
found  in  the  urine.  About  three  months  later  there  were  thirst, 
polyuria,  weariness,  etc.,  and  sugar  was  found  in  the  urine. 

October  20,  1886. — The  quantity  of  urine  was  100  ounces  con- 
taining 31  grains  of  sugar  per  ounce.  The  general  diabetic  symp- 
toms were  marked.  The  patient  was  put  upon  the  antidiabetic  diet 
and  Clemens'  solution.  On  October  2"]  the  quantity  of  urine  was 
reduced  to  40  ounces  and  it  contained  no  sugar.  The  diabetic 
symptoms  had  entirely  disappeared.  November  4  and  27  the  con- 
ditions were  the  same.  The  patient  then  removed  to  the  West. 
On  January  28,  1887  he  wrote  me  that  he  was  perfectly  well.  On 
April  28  he  wrote  that  he  was  as  "  good  as  new."  Since  his  re- 
moval to  the  West  the  urine  has  been  repeatedly  examined  and  no 
sugar  has  been  found.  The  treatment  has  been  continued,  with 
slight  relaxation  in  the  diet. 

Case  LXXVII. — A  gentleman,  twenty-four  years  of  age,  5  feet 
5i  inches  tall,  weighing  132  pounds. 

October  28,  1885. — The  general  diabetic  symptoms  were 
marked.  The  patient  had  lost  twelve  pounds  in  weight  within  the 
past  three  weeks.  The  quantity  of  urine  was  112  ounces  containing 
28  grains  of  sugar  per  ounce.  The  patient  was  put  upon  the  treat- 
ment already  described.  On  January  6,  1886  the  diabetic  symptoms 
had  disappeared  and  the  quantity  of  urine  was  reduced  to  50  ounces 
containing  4  grains  of  sugar  per  ounce.  On  May  19  and  June  30 
the  urine  contained  no  sugar.  On  September  8  the  quantity  of 
urine  was  90  ounces  containing  iii  grains  of  sugar  per  ounce. 
The  diet  had  been  imperfect  for  about  two  months. 

March  2,  1887. — The  urine  was  normal  in  quantity  and  it  con- 
tained 9  grains  of  sugar  per  ounce.  The  patient  had  been  eating 
freely  of  antidiabetic  bread,  which,  as  I  have  stated,  probably 
contained  about  thirty  per  cent,  of  starch. 

Case  LVIII. — A  gentleman,  forty-three  years  of  age,  5  feet  9 
inches  tall,  weighing  204  pounds.  The  disease  is  probably  of  eight 
or  ten  years'  standing,  but  sugar  was  recognized  in  the  urine  only 
one  year  before  the  patient  came  under  my  care. 

November  30,  1884. — The  diabetic  symptoms  were  marked. 
The  urine  was  very  abundant  and  contained  6  grains  of  sugar  per 
ounce.  The  patient  was  put  upon  the  treatment  already  described. 
On  December  13  the  s\mptoms  had  disappeared,  the  urine  was  re- 
duced to  the  normal  daily  quantity  and  there  was  no  sugar. 

July  7,  1885. — The  patient  had  been  perfectly  well.  The  urine 
had  been  examined  seven  times  since  December  13,  1884  and  no 
sugar  was  found.     The  diet  had  been  well  carried  out. 

September  20.  1886. — The  quantity  of  urine  was  55  ounces. 
The  morning  urine  contained  15^  grains  of  sugar  per  ounce  and 
the  evening  urine,  30  grains.  The  diabetic  symptoms  had  returned 
in  a  moderate  degree. 

October  12. — The  urine  was  normal  in  quantity  and  contained 
14^   grains  of  sugar  per  ounce.     The  antidiabetic  treatment  was 


364       MEDICINAL   TREATMENT    OF    DIABETES 

resumed.  The  diet  had  been  unrestricted  since  October,  1885,  the 
patient  then  regarding  himself  as  cured. 

October  16. — The  urine  was  normal  in  quantity  and  contained 
9^  grains  of  sugar  per  ounce. 

November  16. — The  urine  contained  no  sugar  and  the  diabetic 
symptoms  had  disappeared.  On  January  24,  1887  the  conditions 
were  the  same. 

April  13,  1887. — The  urine  contained  li  grain  of  sugar  per 
ounce.  The  patient  had  been  travelling  and  the  conditions  for 
maintaining  an  antidiabetic  diet  were  unfavorable.  The  patient 
had  been  eating  freely  of  antidiabetic  bread. 

The  ten  cases  reported  are  all  that  are  now  under  my 
immediate  observation.  At  the  risk  of  being  tedious,  I 
have  given  certain  details  reganHng  these  cases,  although 
my  records  have  been  considerably  abridged  in  this  article. 
These  cases  seem  to  me  to  be  quite  instructive.  Taken  in 
connection  with  my  other  recorded  cases,  they  lead  me 
to  the  following  conclusions: 

I.  In  the  three  severe  cases  in  which  I  have  used  the 
solution  of  lithium  carbonate  and  sodium  arsenate  in  car- 
bonic acid  water,  no  marked  effects  have  been  observed  in 
the  few  weeks  during  which  the  remedy  has  been  em- 
ployed; but  the  treatment  seems  to  me  to  be  worthy  of 
more  extended  trial  and  it  may  be  useful  in  mitigating  the 
severity  of  a  strict  antidiabetic  diet. 

II.  The  so-called  specifics  for  diabetes  have  little  if  any 
efifect.  An  exception,  however,  may  be  made  in  favor  of 
the  bromide  of  arsenic,  which  has  sometimes  seemed  to  me 
to  control  to  a  slight  extent  the  thirst,  polyuria  and  dis- 
charge of  sugar. 

III.  The  main  reliance  in  treatment  is  to  be  placed 
upon  an  antidiabetic  diet.  This  has  fallen  somewhat  into 
disrepute  because  it  is  seldom  efficiently  carried  out.  In 
no  single  instance,  out  of  ninety-nine  recorded  cases,  have 
I  found  that  the  antidiabetic  diet  had  been  enforced. 

IV.  Milk  should  be  absolutely  interdicted.  Its  influ- 
ence over  the  progress  of  the  disease  is  prompt,  powerful 
and  most  injurious. 

V.  There  are  certain  cases  in  which  dietetic  treatment 
promptly  arrests  the  glycosuria  and  keeps  it  under  con- 
trol. There  are  other  cases  in  which  treatment  seems  to 
be  of  little  avail,  except,  possibly,  in  retarding  the  prog- 
ress toward  a  fatal  result.     Of  the  ten  cases  reported  and 


MEDICINAL   TREATMENT    OF    DIABETES       365 

now  under  observation,  seven  are  amenable  to  treatment 
and  three  are  obstinate. 

VI.  A  confirmed  diabetic  may  be  cured,  in  the  sense 
that  all  symptoms  will  disappear;  but  the  disease  is  likely 
to  return  at  any  time  under  an  unrestricted  diet.  Still, 
moderate  care  in  diet  will  sometimes  secure  immunity. 

VII.  A  patient  who  has  once  had  diabetes  should  have 
his  urine  examined  every  few  weeks.  Glycosuria  always 
precedes  the  general  symptoms  of  the  disease,  and  these 
general  symptoms  may  sometimes  be  forestalled  by  proper 
treatment  employed  so  soon  as  sugar  makes  its  appear- 
ance in  the  urine. 

VIII.  As  the  disease  returns,  either  from  imprudences 
in  diet  or  from  other  causes,  the  successive  recurrences 
present  greater  and  greater  difficulties  in  the  way  of  treat- 
ment. 


XVIII 

THE  INFLUENCE  OF  EXCESSIVE  AND  PRO- 
LONGED MUSCULAR  EXERCISE  ON  THE 
ELIMINATION  OF  EFFETE  MATTERS  BY 
THE   KIDNEYS 

Published  in  the  "  New  York  Medical  Journal  "  for  October,  1870. 

In  the  month  of  May,  1870,  Weston,  the  pedestrian, 
attempted  to  walk  one  hundred  miles  in  twenty-two  con- 
secutive hours.  This  feat  was  to  be  accomplished  in  an 
enclosure  known  as  the  Empire  Skating  Rink;  a  square 
building,  well  ventilated,  in  which  a  rectangular  track  was 
laid  out,  measuring  nearly  one-eighth  of  a  mile.  The 
weather  was  mild  and  clear,  a  pleasant  day  for  that  season 
of  the  year.  This  feat  of  endurance  was  accomplished  in 
twenty-one  hours  and  thirty-nine  minutes.  Attracted  by 
the  interest  felt  in  this  effort,  I  was  present  during  the  last 
three  hours  of  the  walk.  It  is  not  pertinent  to  the  scientific 
questions  involved  to  discuss  the  objections  raised  in  regard 
to  the  exact  measurement  of  the  course,  the  style  of  walk- 
ing, etc.;  suffice  it  to  say  that,  practically,  Weston  made 
one  hundred  miles,  a  few  feet  more  or  less  perhaps,  in  twen- 
ty-two consecutive  hours — a  fact  which  none  interested 
upon  one  side  or  the  other  have  denied.  While  at  the  rink, 
I  ascertained  from  the  superintendent  and  judges  that  all 
of  the  urine  passed  during  the  walk  had  been  collected,  as 
a  mere  matter  of  convenience,  in  a  single  vessel.  This  urine 
I  obtained  entire  and  subjected  it  to  analysis. 

It  is  evident  to  any  physiologist  that  there  is  much 
scientific  interest  attached  to  the  quantitative  analysis  of 
the  urine  passed  during  such  an  expenditure  of  muscular 
and  nerv'ous  force  as  is  involved  in  walking  one  hundre'd 
miles  in  twenty-two  hours:  particularly  in  view  of  the  recent 
observations  of  Fick  and  Wislicenus,  Frankland,  Haughton 
366 


PROLONGED    MUSCULAR    EXERCISE  367 

and  others,  which  seem  to  show  that  muscular  exertion, 
under  certain  conditions  of  diet,  does  not  increase  the 
elimination  of  urea.  This  effort  is  nearly  the  maximum 
of  what  a  person  endowed  with  unusual  powers  of  endur- 
ance is  capable;  and  I  embraced  the  opportunity  of  as- 
certaining what  effect  such  an  amount  of  muscular  exercise 
would  have  upon  disassimilation.  To  give  full  value  to 
my  observations,  it  became  necessary  to  compare  the 
elimination  of  effete  matter  during  the  walk  with  the  daily 
excretion  under  ordinary  conditions.  In  all  points  con- 
nected with  these  investigations,  I  have  had  the  coopera- 
tion of  Weston;  but  his  absence  from  the  city  prevented 
my  procuring  a  specimen  of  the  ordinary  urine  until 
August.  The  specimen  then  obtained,  however,  seemed 
to  me  to  answer  perfectly  for  purposes  of  comparison. 

Prefacing  my  observations  with  the  statement  that  the 
idea  of  entering  upon  them  originated  during  the  last  two 
hours  of  the  walk,  so  that  the  comparison  of  the  urine 
under  exercise  with  the  ordinary  urine  was  necessarily 
made  with  a  specimen  collected  some  time  after,  I  shall 
proceed  to  detail  the  facts  observed  and  to  make  from 
them  such  physiological  deductions  as  seem  to  be  admis- 
sible. All  the  statements  in  regard  to  the  condition,  diet, 
etc.,  have  been  submitted  to  Weston  and  been  carefully 
corrected. 

Weston  is  thirty-one  years  of  age,  of  medium  height 
and  rather  lightly  built,  weighing,  in  ordinary  clothing, 
about  one  hundred  and  thirty  pounds.  Allowing  eight 
pounds  for  clothing,  his  ordinary  weight  would  be  about 
one  hundred  and  twenty-two  pounds.  As  would  be  ex- 
pected of  a  person  of  such  endurance  his  general  health  is 
perfect.  His  habits,  as  regards  eating  and  sleeping,  are 
very  irregular.  He  is  likely  to  be  at  work  all  night,  sleep- 
ing part  of  the  day,  and  his  meals  may  be  taken  at  any 
hour.  He  has  never  been  through  a  regular  system  of 
training  as  a  preparation  for  any  of  his  pedestrian  feats,  but 
simply  takes  moderate  exercise  by  walking.  The  follow- 
ing was  his  condition  at  the  time  of  the  walk: 

The  weight  was  one  hundred  and  seventeen  pounds, 
naked,  allowing  eight  pounds  for  clothing.  This  is  five 
pounds  less  than  his  ordinary  weight.  His  physical  con- 
dition was  perfect.     The  lower  limbs  were  well  developed 


368  PROT,ONGRD    MUSCULAR    EXERCISE 

and   "  fine,"  with  the  chest   and  upper  extremities  very 
lii^ht. 

At  12.15  ^-  M.,  the  walk  was  begun  and  the  hundred 
miles  were  accomplished  in  twenty-one  hours  and  thirty- 
nine  minutes,  ending  at  9.45  p.  m.  At  the  end  of  the  walk 
Weston  did  not  seem  fatigued,  but  appeared  brisk  and 
bright  and  was  as  well  as  ever  on  the  following  day.  No 
urine  was  passed  up  to  10.15  P-  m.;  so  that  the  urine  col- 
lected was  practically  the  urine  of  twenty-two  hours. 

During  the  walk  Weston  took  the  following  articles  of 
food  in  small  quantities  and  at  short  intervals: 

Between  one  and  two  bottles  of  beef-essence;  two  bot- 
tles of  oatmeal-gruel;  sixteen  to  eighteen  eggs,  raw,  in 
water.  He  drank  a  little  lemonade  and  took  water  very 
frequently,  a  mouthful  at  a  time,  only  to  rinse  his  mouth. 
While  walking  the  last  ten  miles  he  took  two  or  three  swal- 
lows of  champagne  and  about  two  and  a  half  fluidounces  of 
brandy  in  ten-drop  doses.  The  head  and  face  were  sponged 
freely  at  short  intervals  and  the  food  and  drink  w^ere  taken 
mainly  on  the  walk. 

All  the  urine  that  was  passed  during  the  walk  w-as 
received  into  a  pail  in  a  little  muslin  enclosure  by  the  side 
of  the  track.  There  was  no  discharge  from  the  bowels  dur- 
ing that  time.  I  have  taken  the  quantity  as  representing 
twenty-two  hours,  and  have  calculated  from  that  the 
quantity  to  represent  twenty-four  hours. 

Air  the  analyses  were  made  by  the  processes  described 
in  my  little  work  on  "  Chemical  Examination  of  the  Urine. '^ 
The  urea  was  estimated  by  Davy's  method  w-ith  hypo- 
chlorite of  soda,  the  French  Labarraque's  solution,  a  so- 
lution which  had  been  carefully  corrected  and  compared 
W'ith  Liebig's  method.  The  chlorine  w-as  estimated  by  a 
graduated  solution  of  nitrate  of  silver;  the  sulphuric  acid, 
by  a  graduated  solution  of  chloride  of  barium;  and  the 
phosphoric  acid,  by  a  graduated  solution  of  sesquichloride 
of  iron.  The  uric  acid  was  estimated  by  actual  weight, 
evaporating  the  urine  to  a  thick  syrup,  extracting  the  urea, 
creatin,  creatinin  and  coloring  matter  wath  absolute  alco- 
hol, setting  free  the  uric  acid  and  extracting  the  inorganic 
salts  with  very  dilute  hydrochloric  acid,  and  collecting  the 
uric  acid  on  a  filter.  The  processes  in  the  analyses  of  both 
specimens  of  urine  w^ere  identical.     The  examination  was 


PROLONGED    MUSCULAR   EXERCISE 


569 


begun  about  fourteen  hours  after  the  last  urine  had  been 
passed.  The  examination  of  the  specimen  taken  for  com- 
parison was  begun  sixteen  hours  after  it  had  been  col- 
lected. 


EXAMINATION    OF    URINE    PASSED    DURING   THE   WALK 

Weight  of  body,  without  clothing,  one  hundred  and 
seventeen  pounds. 

Articles  of  food  and  drink  taken:  Beef-essence,  between 
one  and  two  bottles;  oatmeal-gruel,  two  bottles;  sixteen  to 
eighteen  eggs,  raw,  in  water;  lemonade,  about  half  a  pint; 
champagne,  about  three  fluidounces;  brandy,  two  and  a  half 
fluidounces;  water  to  rinse  the  mouth  every  few  minutes, 
and  but  little  swallowed. 

No  sleep  during  the  twenty-two  hours. 

Table  I. — composition  of  the  urine 

Quantity  in  the  twenty-two  hours,  73^  fluidounces  (esti- 
mated for  twenty-four  hours,  80  fluidounces);  acidity 
normal;  color  rather  light  canary;  odor  strongly  urinous 
but  normal;  specific  gravity,  1011.55;  no  abnormal  mat- 
ters; microscopical  examination  negative. 


Perfluidounce, 


Urea 

Chlorin    

Sulphuric  acid.  . 
Phosphoric  acid  (total)  j  i .  504 
Phosphoric  acid  (with 

alkalis)  * 1.2S0 

Phosphoric  acid  (with 

earths)* 0.224 

Uric  acid I0.500 


5.779  grains, 
1. 120       " 
0.920       " 


In  22  hours. 


424.756  grains. 

82.320  '* 

67.620  " 

110.544  " 

94.060  " 

16.484  " 

36.750  " 


Per  hour. 


In  24  hours. 


19.307  grains. 

3-742  " 

3-074  " 

5.025  " 

4.275  " 

0.750  " 

1.670  " 


463. 36S  grains. 

89.808 

73.776  " 

120.600  " 

102.600  " 

18.000  " 

40.080  " 


On  August  20,  1870  Weston  began  to  collect  for  me 
the  urine  of  the  twenty-four  hours,  from  6  P.  m.,  the  20th, 
to  6  p.  M.,  the  2 1  St.  The  weather  was  warm  but  not  oppres- 
sive. His  habits  of  life  were  about  the  same  as  before  his 
walk  of  May  25.  He  wrote  the  greater  part  of  the  night  of 
the  19th  and  slept  from  4.30  a.  m.  to  8.15  a.  m.  of  the  20th. 


*  Approximative. 


370  PROLONGED    MUSCULAR    EXERCISE 

He  then  went  up  the  Hudson  River,  and  on  the  steamboat 
took  a  light  breakfast  at  1 1  a.  m.,  consisting  of  rare  beef- 
steak, fried  potatoes  and  cokl  bread  with  water.  Between 
that  time  and  3  p.  m.  he  walked  two  miles.  At  3  p.  m.  he 
took  dinner  as  follows:  Broiled  ham  with  eggs,  stewed  to- 
matoes, fried  potatoes  and  sweet  corn,  drinking  one  glass 
of  fresh  milk  and  two  glasses  of  claret  wine  with  water. 
At  5.45  he  ate  of  muskmelon  and  a  few  pears. 

He  began  to  collect  the  urine  at  6  p.  m.  At  7  p.  m.  he 
ate  a  supper  of  pickled  lambs'  tongues  with  warm,  light 
biscuit  and  drank  one  cup  of  tea.  He  slept  from  midnight 
till  7  A.  M.,  then  rose  for  a  moment,  retiring  again  and 
sleeping  until  12  m.  of  the  21st.  At  2  p.  m.  he  ate  a  hearty 
breakfast  (or  diimer)  of  cold  corned  beef,  hot  bread-cakes 
and  one  slice  of  bread  and  drank  one  cup  of  coffee.  He  did 
not  eat  again  until  after  6  p.  m.,  the  limit  of  the  time  for 
collecting  the  urine. 

During  the  afternoon  of  the  21st  he  drank  one  glass  of 
Ottawa  beer  (a  mild,  effervescing  root-beer)  and  smoked 
two  cigars. 

At  II  p.  M.  August  20  he  had  an  evacuation  of  the 
bowels  but  did  not  lose  anv  urine. 


EXAMINATION     OF    THE     URINE     OF    TWENTY-FOUR     HOURS 
UNDER     ORDINARY     CONDITIONS. 

Weight  of  body  without  clothing,  one  hundred  and 
twenty-two  pounds. 

Articles  of  food  and  drink  taken:  Supper — Pickled 
lambs'  tongues,  warm,  light  biscuit,  one  cup  of  tea.  Din- 
ner— Cold  corned  beef,  hot  bread-cakes,  one  slice  of  bread, 
one  cup  of  coffee.  One  glass  of  Ottawa  beer  and  two  cigars 
during  the  day. 

Slept  between  eleven  and  twelve  hours.  Ate  salt  ham 
the  day  before  at  3  p.  m. 

Table  H. — composition  of  the  urine 

Quantity  in  twenty-four  hours,  33  fluidounces;  acidity 
rather  faint;  color  rather  light  canary  and  slightly  turbid; 
odor  strongly  urinous  but  normal;  specific  gravity  1025.43; 
no  abnormal  matters;  decomposed  rather  rapidly;  micro- 


PROLONGED    MUSCULAR    EXERCISE 


371 


scopical  examination  showed  a  rather  unusual  quantity  of 
mucus,  otherwise  negative. 


Urea 

Chlorin 

Sulphuric  acid 

Phosphoric  acid  (total) 

Phosphoric  acid  (with  alkalis)  * . . 
Phosphoric  acid  (with  earths)  *. . 
Uric  acid 


Per  fluidounce. 


5.800  grains. 

3.360 

1.440 

0.960 

0.640 

0.320 

0.680 


Per  hour 


7.975  grams. 

4.620 

i.gSo 

1.320 

0.8S0 

0.440 

0.935 


In  24  hours. 


191.400  grains. 

110.880  " 

47.520  " 

31.680  " 

21.120  " 

10.560  " 

22.440  " 


Table  III. — comparison  of  the  urine  passed  under 

ORDINARY  CONDITIONS  (rEST)  WITH  THE  URINE 
PASSED  DURING  THE  WALK  OF  ONE  HUNDRED  MILES 
IN    TW^ENTY-TW^O    HOURS    (eXERCISE) 


PER    HOUR. 


IN   TWENTY-FOUR    HOURS. 


Rest. 


Total  quantity.  . 

Urea 

Chlorin 

Sulphuric  acid.  . 
Phosphoric    acid! 

(total) 

Phosphoric    acid 

(with  alkalis). 
Phosphoric    acid 

(with  earths). . 
Uric  acid 


1.375  oz. 
7-975  grs 
4.620 
1.980 

1.320 

0.880 

0.440 
0.935 


Exercise. 


Rest. 


3.341  oz.      33.000  OZ.      80, 
19.307  grs.  191.400  grs.  463 


Exercise. 


3-742 
3074 

5.025 

4-275 

0.750 
1.670 


lio.Sbo 
47-520 

31.680 

21.120 

10.560 
22.440 


89 

73 

120 

102 

18 
40 


000  OZ. 

368  grs. 
808    ' 
776    ' 

600    ' 

.600    ' 

000    ' 
.080    ' 


Percentage  of 
difference. 


142.424 

142.094 

19.004 

55-252 

J280.681 
j  365. 800 

70.454 
78.609 


decrease, 
increase. 


The  foregoing  tables  show  the  effects  of  prolonged 
muscular  exercise  upon  the  general  process  of  disassimila- 
tion,  as  indicated  by  the  elimination  of  effete  matters  by 
the  kidneys;  and  this  is  all  the  more  marked  as  the  exertion 
probably  reached  to  near  the  limit  of  endurance.  By 
reference  to  Table  III.  it  will  be  seen  that  the  variations 
under  repose  and  exercise  are  very  great.  It  was  impos- 
sible to  compare  two  specimens  of  the  urine  of  the  twenty- 
four  hours  taken  under  conditions  of  diet  precisely  iden- 
tical, which  would  have  made  the  observations  upon  the 
effects  of  muscular  exercise  much  more  satisfactory;  but 
physiologists  are  now  sufficiently  familiar  with  the  effects 


*  Approximative. 


372  PROLONGED    MUSCULAR   EXERCISE 

of  diet  upon  the  composition  of  the  urine  to  enable  them 
to  separate  tliese  influences  and  appreciate  the  modifica- 
tions produced  l)y  tlie  great  strain  upon  the  muscular 
system.  I  shall  proceed,  therefore,  to  consider  these 
changes,  taking  into  account  the  disturbing  influences  of 
the  variations  in  the  food  and  drink. 

Total  Quantity  of  Urine. — The  quantity  of  water 
in  the  urine  was  much  greater  during  exercise,  the  excess 
over  the  cjuantity  passed  under  ordinary  conditions 
amounting  to  nearly  one  hundred  and  fifty  per  cent.  This 
I  attribute  in  a  measure  to  the  excessive  muscular  exertion 
and  in  part  to  the  large  quantity  of  liquids  taken  and  the 
fact  that  the  skin  did  not  act  very  freely.  It  is  a  fact  that 
an  increase  in  the  water  of  the  urine,  even  when  due  entire- 
ly to  the  ingestion  of  liquids,  increases  the  absolute  quantity 
of  solid  matters  excreted. 

Urea. — The  most  interesting  point  in  connection  with 
these  investigations  relates  to  the  excretion  of  urea;  and  in 
considering  this  it  will  be  necessary  to  consider  the  influ- 
ence of  diet.  By  reference  to  Table  IL,  which  gives  the 
composition  of  the  urine  under  ordinary  conditions,  it  will 
be  seen  that  the  proportion  of  urea  is  smaller  than  one 
would  expect,  judging  from  the  specific  gravity,  but  that 
the  chlorides  are  largely  in  excess.  The  total  quantity  in 
the  twenty-four  hours  is  very  small,  hardly  two  hundred 
grains.  On  inquiry,  I  ascertained  that  Weston  is  a  small 
eater;  and  on  that  day  he  ate  but  twice,  slept  twelve  hours 
and  took  very  little  exercise.  His  diet,  also,  on  that  day 
contained  but  little  nitrogenous  matter.  These  facts 
taken  in  connection  with  his  weight,  which  was  but  one 
hundred  and  twenty-two  pounds,  in  part  account  for  the 
small  quantity  of  urea. 

On  the  day  of  the  walk  the  elimination  of  urea  was 
enormous  in  proportion  to  the  weight  of  the  body,  amount- 
ing to  four  hundred  and  sixty-three  grains,  nearly  one  and 
a  half  times  more  than  on  the  day  of  repose.  The  question 
here  arises  as  to  how  far  this  is  due  to  conditions  of  diet, 
and  what  proportionate  increase  is  to  be  attributed  to  the 
great  muscular  exertion: 

I.  The  excess  of  water  eliminated  by  the  kidneys  would 
account  for  a  small  part,  but  only  a  small  part,  of  the  in- 
crease of  urea. 


PROLONGED    MUSCULAR   EXERCISE  373 

II.  The  diet  on  the  day  of  the  walk  contained  a  large 
amount  of  nitrogenous  matter;  among  other  articles,  six- 
teen to  eighteen  raw  eggs.  This  will  account  for  a  con- 
siderable proportion  of  the  excess  of  urea;  and  it  remains 
to  see  how  much  can  reasonably  be  referred  to  this  source. 

III.  The  most  complete  series  of  observations  upon  the 
effects  of  nitrogenous  food  on  the  elimination  of  urea  are 
those  of  Lehmann.*  In  these  observations,  made  on  his 
own  person,  Lehmann  found  that  he  excreted,  on  a  well- 
regulated  mixed  diet,  501.6  grains  of  urea  in  twenty-four 
hours.  On  a  purely  animal  diet,  taking,  as  one  item,  thirty- 
two  eggs,  he  excreted  821  grains,  an  excess  of  nearly  sixty- 
four  per  cent.  In  the  case  of  Weston,  who  took  about  half 
the  number  of  eggs,  there  was  an  excess  of  one  hundred 
and  forty-two  per  cent.,  leaving  an  excess,  due  to  his  long- 
continued  exertion',  of  seventy-eight  per  cent.  Lehmann 
also  found  that  while  he  took  in  the  eggs  465.5  grains  of 
nitrogen,  he  discharged  only  387.8  grains  of  nitrogen  in  the 
urea. 

I  do  not  propose  to  discuss  critically  the  many  observa- 
tions that  have  been  made  within  the  last  few  years  on  the 
influence  of  muscular.exercise,  conjoined  with  peculiar  diet, 
upon  the  elimination  of  urea.  So  far  as  I  know,  on  no 
occasion  has  this  point  been  investigated  when  the  mus- 
cular exertion  has  been  so  severe  and  prolonged.  There 
can  be  hardly  any  doubt  that  in  the  case  of  Weston  the 
feat  of  endurance  which  he  accomplished  increased  the 
elimination  of  urea  by  seventy-five  or  a  hundred  per  cent. 

Chlorides. — During  the  walk  the  chlorides  in  the 
urine  seemed  to  be  below  the  average,  while  they  were  in 
excess  for  the  day  of  repose.  The  influence  of  the  exercise 
on  the  proportion  of  chlorides  does  not  seem  to  be  very 
marked.  On  the  day  when  the  normal  urine  was  taken, 
the  diet  included  a  considerable  quantity  of  salt  in  the 
corned  beef,  and  on  the  day  before,  salt  ham  was  taken  at 
3  p.  M.,  three  hours  before  the  urine  was  collected.  The 
variations  in  the  chlorides  may  possibly  be  accounted  for 
by  the  diet. 

Sulphates  and  Phosphates. — The  total  quantity  of 
sulphates  was  considerably  increased  during  the  day  of  the 

*  Lehmann,  "  Physiological  Chemistry,"  Philadelphia,  1855,  vol.  i.,  p.  150  f^  seq. 


374  PROLONGED   MUSCULAR   EXERCISE 

walk.  This  is  in  accordance  with  all  observations  on  this 
point. 

The  proportion  of  phosphates  on  the  day  of  the  walk 
was  nearly  quadrupled.  This  is  a  very  interesting  fact,  as 
the  phosphates  constitute  a  large  and  essential  part  of  the 
inorganic  constituents  of  the  tissues.  A  part  of  the  great 
excess  was  probably  due  to  the  muscular  exertion  and 
want  of  sleep,  and  a  part  to  the  large  preponderance  of 
animal  food. 

Uric  Acid. — The  muscular  exertion  increased,  by 
about  seventy-eight  per  cent.,  the  elimination  of  uric  acid; 
but  the  proportion  per  lluidounce  was  less  during  the  exer- 
cise than  in  repose.  The  theory  has  been  advanced  that 
exercise  increases  urea  and  diminishes  uric  acid,  the  latter 
undergoing  oxidation  more  rapidly.  My  observations  are 
not  conclusive  on  this  point.  The  diminution  in  the  pro- 
portion of  uric  acid  per  fluidounce  would  seem  to  show  that 
oxidation  was  more  rapid  under  exercise,  the  immense  in- 
crease in  urea  being  also  an  argument  in  favor  of  this  view. 

In  conclusion,  these  observations  seem  to  show  that 
excessively  severe  and  prolonged  muscular  exercise  in- 
creases largely  the  quantity  of  nitrogenous  excrementi- 
tious  matters  eliminated  in  the  urine,  particularly  urea, 
and  produces  a  corresponding  increase  in  the  elimination 
of  most  of  the  inorganic  salts. 


XIX 

ON  THE  EFFECTS  OF  SEVERE  AND  PRO- 
TRACTED MUSCULAR  EXERCISE  ;  WITH 
SPECIAL  REFERENCE  TO  ITS  INFLUENCE 
ON   THE  EXCRETION   OF   NITROGEN 

Published  in  the  "  New  York  Medical  Journal"  for  June,  1871. 

PART    I 

In  May,  1870  I  had  an  opportunity  of  examining  the 
entire  urine  passed  by  Weston,  the  pedestrian,  during  the 
time  occupied  in  accomphshing  the  feat  of  walking  one 
hundred  miles  in  twenty-one  hours  and  thirty-nine  min- 
utes. The  urine  on  that  occasion  happened  to  have  been 
passed  into  a  single  vessel  and  had  been  undisturbed  until 
it  came  into  my  possession.  I  had  no  means  of  obtaining 
any  reliable  scientific  information  in  regard  to  the  quantity 
and  character  of  the  food  taken  during  that  time,  nor  had 
I  obtained,  for  purposes  of  comparison,  a  specimen  of  the 
urine  passed  on  the  day  before  this  muscular  effort.  It 
was  several  weeks,  indeed,  before  I  could  get  the  urine 
of  twenty-four  hours  of  comparative  repose;  which  I  was 
forced  to  take  as  representing  the  normal  excretion.  I 
simply  took  the  material  for  scientific  analysis  as  I  could 
best  obtain  it  and  published  the  results  with  a  statement 
of  the  facts,  not  at  that  time  entertaining  any  definite  hope 
of  being  able  to  repeat  the  investigations  under  more 
favorable  conditions.  I  was,  of  course,  well  aware  of  the 
necessity  of  carefully  estimating  certain  constituents  of  the 
food,  and  of  comparing  the  elimination  of  efifete  matters, 
particularly  those  containing  nitrogen,  with  the  matters 
ingested.  Had  I  been  sure  of  an  opportunity  to  study 
the  effects  upon  excretion  of  excessive  and  prolonged  mus- 
cular exercise,  such  as  has  since  presented  itself,  my  first 

375 


376  EXCRETION   OF    NITROGEN 

experiments,  of  the  unavoidable  defects  of  which  no  one 
could  be  more  sensible  than  1,  would  not  have  been 
published.  My  first  observations  have  been  excluded  in 
the  present  inquiry  on  account  of  the  imperfect  data  on 
which  they  were  based;  but  1  may  anticipate  my  conclu- 
sions from  these  more  complete  experiments  far  enough 
to  state  that  the  results  have  been  essentially  the  same. 

In  the  summer  of  1870  Weston  proposed  to  make  an 
attempt  to  walk  four  hundred  miles  in  five  consecutive 
days  and  upon  one  of  those  days  to  walk  one  hundred  and 
twelve  miles  in  twenty-four  consecutive  hours.  He  offered 
to  submit  himself  to  any  scientific  observations  that  I 
might  wish  to  undertake  in  connection  with  this  effort. 
This  offer  was  accepted;  and  I  have  endeavored  to  make 
this  occasion  to  the  fullest  extent  useful  to  physiological 
science.  The  investigations  to  be  made  seemed  to  me  of 
such  importance,  particularly  in  the  present  unsettled  state 
of  opinion  upon  some  points  connected  with  nutrition 
and  disassimilation,  that  I  asked  the  aid  of  certain  well- 
known  scientists,  in  formulating  and  carrying  out  a  series 
of  experiments  which  should  be  as  complete  as  possible. 

The  following  gentlemen  consented  to  lend  to  the  pro- 
posed work  the  advantage  of  their  scientific  experience 
and  judgment:  Dr.  R.  Ogdcn  Doremus,  Professor  of 
Chemistry  in  the  Bellevue  Hospital  Medical  College  and 
in  the  College  of  the  City  of  New  York;  Dr.  J.  C.  Dalton, 
Professor  of  Physiology  in  the  College  of  Physicians  and 
Surgeons;  and  Dr.  W.  H.  Van  Buren,  Professor  of  the 
Principles  of  Surgery,  etc.,  Dr.  Austin  Flint,  Professor  of 
the  Principles  and  Practice  of  Aledicine,  and  Dr.  Alexan- 
der B.  Mott,  Professor  of  Surgical  Anatomy,  all  of  the 
Bellevue  Hospital  ]\Iedical  College. 

At  a  meeting  held  some  weeks  before  the  walk  a  definite 
plan  of  investigations  was  agreed  upon.  Prof.  Doremus 
assumed  the  responsibility  of  all  of  the  necessary  chemical 
analyses,  and  I  proposed  to  take  charge  myself  of  the  re- 
maining scientific  work  and  to  superintend  the  records  of 
diet,  etc.  The  plan  of  operations  agreed  upon  will  be  fully 
detailed  farther  on,  as  an  introduction  to  an  account  of 
our  observations;  but  this  may  be  anticipated  at  the  outset 
by  a  few  general  statements. 

It  was  proposed  to  make  our  observations  for  three 


EXCRETION    OF    NITROGEN 


377 


distinct  periods;  viz.,  first  period,  five  days  before  the  walk; 
second  period,  the  five  days  of  the  walk;  third  period,  five 
■days  after  the  walk.  For  the  fifteen  days  during  which 
Weston  was  to  be  under  observation,  it  was  proposed  to 
have  a  trusty  assistant  with  him  every  instant,  day  and 
night,  who  was  to  weigh  his  food  and  drink  and  make  notes 
under  the  direction  of  one  of  our  number.  This  was  done 
by  Mr.  Thomas  C.  Doremus,  Jr.,  who  performed  his  task 
in  the  most  faithful  and  accurate  manner.  The  urine  and 
feces  were  sent  to  the  laboratory  of  Prof.  Doremus,  where 
they  were  analyzed  under  his  direction  by  his  assistant, 
j\Ir.  Oscar  Loew.  The  necessary  analyses  of  food  were 
also  made  by  Mr.  Loew. 

The  material  thus  collected,  with  a  complete  record  of 
the  walk,  finally  passed  into  my  hands  for  classification 
and  analysis.  Before  this  report  was  written,  the  tables  of 
food,  composition  of  urine,  feces,  etc..  were  calculated. 
This  alone  has  been  a  labor  of  several  weeks,  and  no  pains 
has  been  spared  to  secure  entire  accuracy.  The  numerical 
calculations  were  all  made  by  two  or  more  different 
methods,  so  that  it  has  seemed  almost  impossible  that  any 
error  of  importance  should  have  been  overlooked.  Tak- 
ing, as  I  have,  the  bare  records  and  analyses  made  by  ]\Ir. 
Doremus  and  Mr.  Loew,  with  entire  ignorance  of  their 
probable  results,  the  calculations  proceeded  steadily  to 
their  mathematical  conclusions,  which  were  apparent  only 
at  the  time  of  their  actual  completion. 

In  the  preparation  of  this  paper  I  have  attempted  to 
present  the  scientific  data  in  such  a  form  as  to  be  easily 
available  as  ascertained  facts,  to  any  who  may  not  admit 
the  interpretation  I  have  put  upon  them. 

It  may  serve  to  make  the  bearing  of  our  observations 
more  easily  comprehended  to  give  a  succinct  statement  of 
the  generally-received  physiological  views  regarding  cer- 
tain of  the  points  involved.  In  this  I  do  not  propose  to 
analyze  the  literature  of  the  subject,  even  for  the  past  few 
years;  and  I  desire  especially  to  avoid  controversial  dis- 
cussion. I  do  not  intend  to  criticise  the  experiments  of 
others  or  to  point  out  their  defects,  except  in  so  far  as 
these  defects  may  seem  to  be  supplied  by  my  more  ex- 
tended opportunities  for  investigations  in  particular  direc- 
tions. 

25 


378  EXCRETION    OF    NITROGEN 

VIEWS  OF  PHYSIOLOGISTS  IN  REGARD  TO  THE  INFLU- 
ENCES OF  EXERCISE,  DIET,  ETC.,  UPON  THE  ELIMINA- 
TION OF  NITROGENOUS  EXCREMENTITIOUS  MATTERS, 
CHIEFLY    UREA 

Following  the  researches  of  Lavoisier  on  the  chemical 
phenomena  of  respiration  and  their  relations  to  animal 
heat,  the  theories  of  Liebig,  who  divided  the  food  into  two 
classes,  plastic  and  calorific,  were  almost  universally  ac- 
cepted by  physiologists.  Liebig  advanced  the  view  that 
the  articles  of  food  composed  of  carbon,  hydrogen  and  oxy- 
gen, were  chiefly  if  not  entirely  useful  in  maintaining  the 
animal  temperature,  by  entering  into  combination  with  the 
oxygen  of  the  inspired  air,  producing  carbonic  acid,  water 
and  heat.  He  regarded  the  food  composed  of  carbon, 
hydrogen,  oxygen  and  nitrogen  as  concerned  chiefly,  if 
not  entirely,  in  repairing  the  waste  of  the  nitrogenous  parts 
of  the  living  body,  particularly  the  muscular  tissue.  Apply- 
ing these  views  to  muscular  action,  Liebig  assumed  that 
exercise  was  always  attended  with  an  increased  activity  in 
the  destructive  metamorphosis  of  the  nitrogenous  sub- 
stance of  the  muscular  tissue;  and  that  this  could  be  meas- 
ured by  the  quantity  of  urea  excreted.  The  following  is 
a  quotation  from  one  of  his  earlier  works: 

"  Boiled  and  roasted  flesh  is  converted  at  once  into  blood ; 
while  the  uric  acid  and  urea  are  derived  from  the  metamorphosed 
tissues.  The  quantity  of  these  products  increases  with  the  rapidity 
of  transformation  in  a  given  time,  but  bears  no  proportion  to  the 
amount  of  food  taken  in  the  same  period.  In  a  starving  man,  who 
is  any  way  compelled  to  undergo  severe  and  continued  exertion, 
more  urea  is  secreted  than  in  the  most  highly-fed  individual  if  in 
a  state  of  rest."  * 

Again,  Liebig  makes  the  general  statement  that  "  the 
amount  of  tissue-metamorphosis  in  a  given  time  may  be 
measured  by  the  quantity  of  nitrogen  in  the  urine."  f 

For  many  years  this  view  of  the  source  of  the  nitro- 
genous excrementitious  matters  and  the  laws  which  reg- 
ulate the  activity  of  their  production  was  received  by 
physiologists  almost  without  question.  It  was  modified, 
however,  a  few  years  later  by  the  researches  of  Lehmann; 
who  showed  by  a  large  number  of  observations  on  his  ow^n 

*  Liebig,  "  Animal  Chemistry,  or  Chemistry  in  its  Applications  to  Physiol- 
ogy and  Pathology,"  London,  1843,  p.  138.  \  Ibid.,  p.  245. 


EXCRETION    OF    NITROGEN 


379 


person  that,  other  conditions  being  equal,  the  character 
and  quantity  of  food  modified  very  greatly  the  elimination 
of  urea,  as  is  seen  in  the  following  quotation: 

"  My  experiments  show  that  the  amount  of  urea  which  is  ex- 
creted is  extremely  dependent  on  the  nature  of  the  food  which  has 
been  previously  taken.  On  a  purely  animal  diet,  or  on  food  very 
rich  in  nitrogen,  there  were  often  two-fifths  more  urea  excreted 
than  on  a  mixed  diet;  while,  on  a  mixed  diet,  there  was  almost 
one-third  more  than  on  a  purely  vegetable  diet;  while,  finally,  on  a 
non-nitrogenous  diet,  the  amount  of  urea  was  less  than  half  the 
quantity  excreted  during  an  ordinary  mixed  diet."  * 

Lehmann  further  states,  however,  that  upon  a  uniform 
diet  the  elimination  of  urea  is  increased  by  muscular  ex- 
ercise. 

The  views  of  Liebig,  modified  by  the  researches  of  Leh- 
mann, were  pretty  generally  accepted  up  to  1866;  not- 
withstanding that  Bischoff  had  advanced  experiments  to 
show  that  the  elimination  of  nitrogen  by  the  kidneys  was 
regulated  almost  entirely  by  the  quantity  of  nitrogen  in 
the  ingesta.f 

In  1866  Fick  and  Wislicenus  published  an  account  of 
experiments  made  in  ascending  one  of  the  Alpine  peaks, 
the  Faulhorn,  about  6,500  feet  high.  These  experiments 
were  undertaken  with  the  view  of  showing  that  severe  and 
prolonged  muscular  effort  could  be  accomplished  upon 
a  non-nitrogenous  diet.  The  two  experimenters  took 
no  proteid  food  from  midday  on  August  29  until  7  p.  m. 
of  August  30.  The  experiments  proper  began  on  the 
evening  of  the  29th,  at  a  quarter  past  6  p.  m.,  with  a 
complete  evacuation  of  the  bladder.  The  urine  from  this 
time  till  ten  minutes  past  five  on  the  morning  of  the  30th 
(about  eleven  hours)  was  collected  and  called  the  "  night- 
urine."  The  ascent  began  at  ten  minutes  past  five  and 
occupied  eight  hours  and  ten  minutes.  The  urine  passed 
during  this  period  was  collected  as  "  work-urine."  The 
urine  for  five  hours  and  forty  minutes  after  the  ascent 
w'as  collected  as  "  after-work  urine."  The  urine  from  7 
p.  M.,  August  30  till  half-past  five  a.  m.,  xA.ugust  31  w-as 

*  Lehmann,  "  Physiological  Chemistry,"  Philadelphia,  1855,  vol.  i.,  p.  150. 

f  Bischoff,  "  Der  Harnstoff  als  Maas  des  Stoffwechsels,"  Giessen,  1853.  In 
i860  these  researches  were  considerably  extended  by  Bischoff  and  Voit, 
Bischoff  und  Voit,  "  Die  Gesetze  der  Ernahrung  des  Fleischfressers,"  Leipzig 
und  Heidelberg,  i860. 


38o  EXCRETION    OF    NITROGEN 

collected  and  designated  as  "  night-urine."  The  results 
of  the  examinations  of  these  specimens  in  the  two  persons 
were  nearly  identical.  The  following  is  the  estimate  of  the 
elimination  of  nitrogen  per  hour  during  the  different 
periods:  * 

Fick.  Wislicenus. 

During  the  night,  29th  to  30th. .  0.63  grammes.  0.61  grammes. 

During  the  time  of  work 0.41  "  o-39         " 

During  rest  after  work 0.40         "  0.40         " 

During  the  night,  30th  to  31st.  .  0.45  "  0.51  " 

From  these  results  Fick  and  Wislicenus  conclude  that 
muscular  exercise  does  not  necessarily  increase  the  elimi- 
nation of  nitrogen;  that  the  substance  of  the  muscle  itself 
is  consumed  in  insignificant  quantity;  and  that  the  mus- 
cular system  is  a  machine,  consuming  in  its  work,  not  its 
own  substance,  but  fuel,  which  is  supplied  by  the  food. 
The  most  efficient  fuel  Fick  and  Wislicenus  consider  to 
be  non-nitrogenous  food;  the  results  of  its  consumption 
being  force,  or  work,  heat  and  carbonic  acid.  They  adopt 
the  view  "  that  the  substances,  by  the  burning  of  which 
force  is  generated  in  the  muscles,  are  not  the  albuminous 
constituents  of  the  tissues,  but  non-nitrogenous  substances, 
either  as  fats  or  hydrates  of  carbon." 

"We  might  express  this  doctrine  by  the  following  simile:  A 
bundle  of  muscle-fibres  is  a  kind  of  machine  consisting  of  albumi- 
nous material,  just  as  a  steam-engine  is  made  of  steel,  iron,  brass, 
etc.  Now,  as  in  the  steam-engine  coal  is  burnt  in  order  to  pro- 
duce force,  so,  in  the  muscular  machine,  fats  or  hydrates  of  carbon 
are  burnt  for  the  same  purpose.  And  in  the  same  manner  as  the 
constructive  material  of  the  steam-engine  (iron,  etc.)  is  worn  away 
and  oxidized,  the  constructive  material  of  the  muscle  is  worn  away, 
and  this  wearing  away  is  the  source  of  the  nitrogenous  constitu- 
ents of  the  urine.  This  theory  explains  why,  during  muscular 
exertion,  the  excretion  of  the  nitrogenous  constituents  of  the  urine 
is  little  or  not  all  increased,  while  that  of  the  carbonic  acid  is 
enormously  augmented ;  for,  in  a  steam-engine,  moderately  fired 
and  ready  for  use,  the  oxidation  of  iron,  etc.,  would  go  on  tolerably 
equably,  and  would  not  be  much  increased  by  the  more  rapid  firing 
necessary  for  working,  but  much  more  coal  would  be  burnt  when 
it  was  at  w^ork  than  when  it  was  standing  idle."t 

I  have  made  these  quotations  from  the  paper  of  Fick 
and  Wislicenus  for  the  reason  that  the  theories  advanced 

*  Fick  and  Wislicenus,  "  On  the  Origin  of  Muscular  Power." — "  London, 
Edinburgh  and  Dublin  Philosophical  Magazine,"  London,  January-June,  1866, 
vol.  xxxi.,  p.  492.  ■)•  Loc.  cit.,  p.  501. 


EXCRETION    OF    NITROGEN  381 

and  the  experiments  reported  have  changed  very  materially 
the  current  of  physiological  opinion  in  regard  to  the  ori- 
gin of  muscular  force  and  the  significance  of  the  elimina- 
tion of  nitrogen.  The  question  is  not  materially  modified 
or  advanced  by  the  papers  of  Frankland  *  or  of  Haughton.f 
who  sustain  fully  the  views  of  Fick  and  Wislicenus,  which 
are  now  adopted  very  largely,  particularly  in  Germany  and 
England. 

The  opposite  view,  that  the  elimination  of  nitrogen  is 
to  a  great  extent  a  measure  of  the  waste  of  the  nitrogenous 
constituents  of  the  tissues  and  that  this  is  increased  by 
exercise,  is  substantially  the  one  advanced  by  Liebig.  Al- 
most all  observers  who  have  experimented  on  the  influence 
of  exercise  upon  the  elimination  of  urea,  under  an  ordinary 
diet,  have  found  its  excretion  markedly  increased.  In 
1867  experiments  were  made  by  Parkes  upon  two  soldiers, 
with  the  view  of  controlling  the  experiments  of  Fick  and 
Wislicenus  by  observations  upon  a  more  extended  scale. :{: 
These  experiments  failed  to  confirm  those  of  Fick  and 
Wislicenus.  They  were  continued  for  a  period  of  eighteen 
days  and  certainly  seemed  to  show  an  increase  in  the  urea, 
attributable  to  muscular  exercise.  The  extraordinary  ex- 
ercise taken  was  a  walk  of  23.70  miles  on  one  day  and 
32.78  miles  on  the  day  following.  During  these  two  days, 
on  an  exclusively  non-nitrogenous  diet,  the  elimination  of 
nitrogen  was  slightly  increased  over  a  period  of  two  days 
of  rest  and  non-nitrogenous  diet.  In  an  analysis  of  a  recent 
course  of  lectures  delivered  by  Dr.  Parkes  at  the  College 
of  Physicians,  London,  it  appears  that  he  is  disposed  to 
take  a  view  of  the  subject  between  the  two  extremes;  viz., 
that  the  muscular  system  is  able  to  accomplish  work  by  the 
consumption  of  non-nitrogenous  food;  that  exercise  does, 
however,  slightly  increase  the  elimination  of  urea  and  that 
during  exercise  a  small  portion  of  the  muscular  substance 
is  consumed;  but  he  is  of  the  opinion  that  the  variations 

*  Frankland,  "  On  the  Origin  of  Muscular  Power." — "  London,  Edinburgh 
and  Dublin  Philosophical  Magazine,"  London,  July-December,  1866,  vol. 
xxxii.  p.  1S2,  et  seq. 

\  Haughton,  "  Address  on  the  Relation  of  Food  to  Work  done  by  the  Body, 
and  its  Bearing  upon  Medical  Practice." — "  The  Lancet,"  London,  August  15, 
August  22,  and  August  2g,  1868. 

X  Parkes,  "On  the  Elimination  of  Nitrogen  by  the  Kidneys  and  Intestines, 
during  Rest  and  Exercise,  on  a  Diet  without  Nitrogen." — "Proceedings  of  the 
Royal  Society,"  London,  1S67,  vol.  xv..  No.  89,  p.  339  et  seq. 


3S2  EXCRETION   OF    NITROGEN 

in  the  (juantity  of  nitrogen  eliminated  are  almost  entirely 
dependent  upon  the  quantity  of  nitrogen  contained  in  the 
food.* 

One  desirous  of  consulting  further  the  literature  of  this 
question  may  find,  in  a  recent  article  by  Liebig,  a  full  dis- 
cussion of  the  subject  of  the  source  of  muscular  power  from 
his  own  point  of  view.f  He  analyzes  very  fully  the  ex- 
periments of  Parkes,  and  he  finds  in  the  results  fresh  testi- 
mony in  favor  of  his  view  that  the  increase  in  the  elimina- 
tion of  nitrogen  as  a  consequence  of  muscular  exercise  is 
not  limited  to  the  period  of  exertion  but  continues  for  some 
time  after.  On  the  other  hand,  Voit  has  lately  published 
an  elaborate  paper  reviewing  the  publications  on  this  ques- 
tion that  have  appeared  during  the  last  twenty-five  years. :|: 
Neither  of  these  papers  adds  to  the  sum  of  physiological 
knowledge  l)y  the  contribution  of  new  experimental  facts; 
but  they  are  interesting  as  expressing  the  arguments  upon 
two  opposite  sides,  and  they  illustrate  the  necessity  of  new^ 
observations,  in  which  some  of  the  important  omissions  in 
the  experiments  hitherto  made  may  be  supplied. 

PLAN    OF    THE    INVESTIGATIONS    AND    THE    PROCESSES 
EMPLOYED 

A  few  weeks  before  Weston  put  himself  under  our 
observation,  he  was  made  to  undergo  a  thorough  physical 
examination  at  the  hands  of  Prof.  Austin  Flint,  and  his 
urine  was  examined  by  myself.  The  result  showed  that 
Weston  was  in  perfect  health,  at  least  so  far  as  could  be 
determined  by  any  ordinary  physical  examination.  This 
examination  was  made  in  order  to  ascertain  whether  or 
not  there  existed  any  physical  reason  why  it  would  be 
unsafe  for  Weston  to  undertake  his  proposed  task. 

Having  ascertained  that  Weston  was  in  perfect  health, 
he  was  invited  to  be  present  at  a  meeting  for  the  purpose 
of  fixing  upon  a  definite  plan  of  investigation.  At  this 
meeting  were  present.  Profs.  Doremus,  Dalton,Van  Buren, 

*  "  Abstract  of  the  Croon ian  Lectures  delivered  at  the  College  of  Physicians 
by  Dr.  Parkes." — "  Medical  Times  and  Gazette,"  London,  March  15,  iSyi.p.  348. 

f  Liebig,  "  The  Source  of  Muscular  Power." — "  The  Pharmaceutical  Jour- 
nal and  Transactions,"  London,  1S70,  Third  Series,  part  ii.,  p.  161,  and  part 
lii.,  pp.  181,  201,  221. 

i  Voit,  "  Ueber  die  Entwicklung  der  Lehre  von  der  Quelle  der  Muskel- 
k:raft  und  einiger  Theile  der  Ernahrung  seit  25  Jahren." — "  Zeitschrift  fiir 
Biologic,"  MUnchen,  1870,  Bd.  vi.,  S.  305  et  seq. 


EXCRETION    OF    NITROGEN  383 

Flint  and  myself.  Weston  was  here  subjected  to  another 
examination  with  reference  to  his  physical  condition,  which 
was  found  to  be  perfect. 

As  the  result  of  our  deliberations  at  this  meeting  it  was 
decided  to  confine  our  investigations  within  limits  that 
would  render  it  possible  to  complete  them  accurately  and 
satisfactorily;  the  fear  being  that  in  attempting  to  do  too 
much  the  value  of  our  results  might  be  impaired.  It  was 
also  deemed  proper  to  take  the  position  that  we  would 
under  no  circumstances  interfere  with  Weston's  diet,  train- 
ing or  manner  of  making  the  walk,  simply  observing  the 
facts  according  to  our  plan.  This  was  fully  carried  out. 
Throughout  the  entire  fifteen  days  during  which  Weston 
was  under  observation,  he  acted  in  everything  according 
to  his  own  judgment;  and  the  walk  was  made  without  any 
advice  or  interference  on  the  part  of  any  of  those  engaged 
in  the  investigations. 

In  collecting  our  material  it  was  determined  to  note 
the  following  points: 

I.  To  take  our  observations  during  three  periods;  viz., 
a  first  period,  five  days  before  the  walk;  a  second,  the  five 
days  of  the  walk;  and  a  third,  five  days  after  the  walk.  In- 
asmuch as  we  proposed  to  assume  the  entire  responsibility 
of  the  accuracy  of  all  the  facts  noted,  it  was  determined  to 
place  Weston  in  the  hands  of  Mr.  Thomas  C.  Doremus,  Jr., 
son  of  Prof.  Doremus,  who  was  not  to  leave  him,  night  or 
day,  without  notifying  the  person  in  charge  of  the  investi- 
gations. ]\Ir.  Doremus  was  actually  with  Weston,  night 
and  day,  for  the  fifteen  days,  except  on  two  occasions. 
On  one  day,  for  a  few  hours.  Mr.  Doremus'  place  was  sup- 
plied by  Mr.  Loew,  assistant  to  Prof.  Doremus,  who  was 
engaged  in  making  the  chemical  analyses.  On  another 
occasion,  Mr.  Doremus  was  relieved  by  me  for  about  four 
hours.  During  the  walk.  Prof.  Mott,  Prof.  Doremus  and 
I,  one  or  all  of  us,  were  constantly  present  at  the  rink. 
]\Ir.  Doremus  was  with  Weston  almost  constantly  at  this 
time,  but  he  occasionally  slept  in  the  building,  when  Wes- 
ton was  walking  at  night,  leaving  him  in  charge  of  one  of 
us.  It  is  necessary  to  make  these  statements,  in  view  of 
the  extraordinary  character  of  our  results,  to  show  that 
nothing  is  taken  as  a  fact  to  work  upon  unless  obser\^ed 
by  ourselves  or  our  assistants. 


3S4  EXCRETION    OF   NITROGEN 

II.  To  take  every  day,  as  nearly  as  possible  at  the  same 
hour  and  under  the  same  conditions,  the  naked  weight, 
})nlse,  respirations  and  temperature. 

III.  To  note  accurately  the  weight  of  every  separate 
article  taken  as  food  or  drink.  This  was  done  for  two  pur- 
poses: to  note  the  ingesta  and  excreta,  with  reference  to 
the  weight  of  the  body;  and  to  have  all  the  articles  of  food 
separately  weighed,  so  as  to  estimate  the  daily  consumption 
of  nitrogen. 

IV.  To  note  the  amount  of  exercise  taken  each  day, 
in  the  first  period,  before  the  walk,  and  in  the  third  period 
after  the  walk;  and  also  to  note  anything  unusual  with 
reference  to  his  general  condition. 

V.  To  collect  the  entire  urine  of  the  twenty-four  hours,, 
day  by  day,  for  the  purpose  of  subjecting  it  to  chemical 
and  microscopical  examination.  As  Weston  proposed  to 
arrange  in  his  walk  of  five  days  that  the  time  should  expire 
a  few  minutes  after  midnight,  the  twenty-four  hours  for 
collecting  the  urine  were  calculated  from  midnight  to  mid- 
night.    It  was  also  decided  to  collect  and  w'eigh  the  feces. 

In  the  execution  of  the  above  plan  I  assumed  the  re- 
sponsibility of  superintending  the  records,  except  the  notes 
of  the  chemical  analyses,  and  of  making  microscopical  ex- 
aminations of  the  urinary  sediments.  Prof.  Doremus  as- 
sumed the  responsibility  of  the  chemical  analyses.  So  far 
as  the  general  records  are  concerned,  I  have  no  hesitation 
in  testifying  to  their  entire  accuracy.  It  is  fortunate  that 
no  accident  happened,  such  as  the  breaking  of  a  bottle  or 
a  glass,  and  the  only  error  was  in  taking  the  weight  on 
November  23,  the  third  day  of  the  walk.  Prof.  Doremus 
is  equally  satisfied  in  regard  to  the  chemical  analyses  made 
by  his  assistant,  Mr.  Oscar  Loew\ 

The  details  of  the  plan  as  it  was  carried  out  are  as  fol- 
lows : 

Mr.  Doremus,  Mr.  Loew  and  I  were  each  provided 
with  a  notebook.  My  own  notebook  was  for  recording 
the  microscopical  examinations  of  the  urinary  sediments. 

The  following  directions  were  written  in  the  notebook 
given  to  Mr.  Doremus: 

At  ever\^  meal  weigh  the  food  and  drink  in  the  follow- 
ing manner: 

Put  the  meat  on  a  separate  plate  and  weigh  the  plate 


EXCRETION    OF    NITROGEN  385 

before  and  after  eating.  Note  the  loss  of  weight,  which  will 
give  the  quantity  actually  consumed.  Weston  does  not 
intend  to  eat  much  fat,  but  expects  to  get  his  fat  from 
butter.     When  he  eats  fat  it  is  to  be  noted. 

Put  each  vegetable  on  a  separate  plate  and  determine 
the  quantity  consumed,  in  the  same  way  as  for  the  meat. 

Estimate  the  bread  in  the  same  way  as  the  meat  and 
vegetables. 

Take  a  known  weight  of  butter  and  weigh  each  night 
to  ascertain  the  quantity  taken  during  the  day.  It  will  be 
sufficient  to  determine  in  this  way  the  quantity  of  butter 
consumed  in  the  twenty-four  hours. 

Estimate  the  quantity  of  sugar  taken,  in  the  same  way 
as  for  the  butter. 

Note  the  number  of  eggs  taken  and  see  that  they  are 
entirely  consumed. 

Measure  the  water  taken,  by  fluidounces.  and  always 
carry  a  graduated  glass  for  Weston  to  drink  from,  so 
that  the  quantity  shall  be  taken  exactly. 

Measure  the  coffee,  tea  and  any  other  liquids  taken,  in 
the  same  way,  and  note  especially  the  quantity  of  milk 
used. 

Each  night,  just  before  Weston  goes  to  bed,  take 
the  weight  of  the  body,  naked,  the  temperature  under  the 
tongue,  the  pulse  and  respirations,  and  note  the  time  when 
the  above-mentioned  conditions  are  observed.  The  pulse 
is  always  to  be  counted  sitting.  The  respirations  are  to 
be  taken  in  the  same  position,  when  Weston's  attention  is 
diverted  and  when  he  is  perfectly  tranquil. 

Note  the  exercise,  miles  walked,  time,  etc.,  for  each 
twenty-four  hours. 

Collect  all  the  urine  for  each  twenty-four  hours.  Send 
six  fluidounces  to  me  for  microscopical  examination  and 
send  the  remainder  to  the  chemical  laboratory  for  quantita- 
tive analysis.  Before  any  of  the  urine  is  sent,  mix  the  whole 
for  the  twenty-four  hours  and  note  on  the  bottle  sent  to 
the  chemical  laboratory  the  quantity  taken  out  for  micro- 
scopical examination,  so  that  the  chemist  may  take  this  into 
account  in  his  record  of  the  entire  quantity. 

Collect  the  feces  and  send  them  each  day  to  the  chem- 
ical laboratory. 

At  the  end  of  each  record  for  the  day,  note  the  general 


386  EXCRETION    OF    NITROGEN 

condition  of  health  and  feehngs  and  any  unusual  circum- 
stance that  may  have  occurred  during  the  day  affecting  the 
physiological  conditions. 

Note  each  fact  instantly,  leaving  nothing  to  the  memory. 
Read  these  directions  carefully  every  night  before  closing 
the  record  for  the  day  and  supply  at  once  any  omissions. 

The  following  directions  were  written  in  the  notebook 
given  to  Mr.  Loew: 

Measure  the  entire  quantity  of  urine  in  the  twenty-four 
hours. 

Note  the  odor,  color,  reaction  and  specific  gravity. 

Note  the  presence  or  absence  of  albumin  or  sugar. 

Ascertain  the  proportions  of  various  constituents  of  the 
urine,  according  to  directions  received  from  Prof.  Dore- 
mus. 

Be  careful  to  note  each  day  accurately  from  midnight 
to  midnight. 

The  weight  was  taken  each  night,  generally  in  my  pres- 
ence, by  Mr.  Doremus,  as  near  midnight  as  practicable, 
upon  new  platform-scales,  weighing  accurately  to  a  quar- 
ter of  a  pound.  The  food  was  weighed  upon  a  new  balance, 
weighing  accurately  to  iz  of  an  ounce.  These  balances 
were  selected  on  account  of  their  accuracy  and  their  avail- 
ability for  rapid  weighing,  inasmuch  as  it  was  desirable  to 
annoy  Weston  as  little  as  possible,  particularly  in  giving 
him  his  w-eighed  food.  The  pulse,  respirations  and  tem- 
perature w^ere  noted  by  me,  except  on  the  evening  of  No- 
vember 1 6th,  when  they  were  noted  by  Prof.  Dalton.  The 
temperature  was  taken  under  the  tongue  with  a  maximum 
thermometer,  graduated  to    ro  of  a  degree  Centigrade. 

The  weight  of  the  food  w^as  taken  in  the  manner  indi- 
cated. The  liquids  were  measured  in  a  graduated  glass, 
as  a  matter  of  convenience;  but  their  weights  were  calcu- 
lated in  the  final  tables. 

Having  taken  the  weight  of  each  article  of  food,  it  was 
•desired  to  ascertain  the  quantity  of  nitrogen  in  the  ingesta. 
After  consulting  the  works  at  my  command  giving  analyses 
of  different  articles  of  food,  I  compiled  the  following  table 
from  Payen.  It  was  at  first  thought  desirable  to  subject 
specimens  of  each  article  to  analysis  for  nitrogen;  but  the 
conditions  under  which  the  observations  were  carried  out 
seemed  to  render  the  estimates  of  Payen  quite  as  useful. 


EXCRETION    OF    NITROGEN  387 

It  was  assumed  at  the  outset  that  we  were  not  to  interfere 
with  the  diet  in  any  way,  noting  only  the  articles  taken, 
Weston's  food  was  taken  at  several  different  places  and 
was  prepared  by  different  persons;  and  it  would  have  been 
impossible  to  have  analyzed  actual  specimens  of  each  arti- 
cle. In  view  of  this  fact,  it  seemed  probable  that  the  varia- 
tions from  our  analyses,  should  we  have  made  them,  would 
have  been  as  considerable  as  the  variations  from  the  average 
estimates  given  by  Payen.  It  has  been  ascertained,  also, 
that  the  flesh  of  different  animals  presents  but  a  small  frac- 
tion of  a  percentage  of  difference  in  the  nitrogen.  All  the 
meats,  therefore,  are  classed  together  in  the  table  and  are 
assimilated  to  the  composition  of  cooked  beef,  which  con- 
tains about  3.5  per  cent,  of  nitrogen.*  No  estimate  could 
be  found  of  the  proportion  of  nitrogen  in  the  beef-essence, 
head-cheese  or  oatmeal-gruel;  and  these  articles  were  ana- 
lyzed for  nitrogen  by  Mr.  Oscar  Loew,  by  the  ordinary 
method;  viz.,  treating  the  dry  residue  after  evaporation  with 
soda-lime  and  determining  the  nitrogen  as  ammoniochlo- 
ride  of  platinum,  reducing  the  metallic  platinum  by  heat. 
The  estimates  of  the  proportions  of  nitrogen  in  the  food 
were  therefore  approximative;  but  the  percentage  that 
might  properly  be  allow^ed  for  error  would  be  very  slight. 
Even  if  this  should  be  taken  at  the  almost  impossible  figure 
of  ten  per  cent.,  it  would  not  modify  the  results.  The  ad- 
vantage of  experimenting  upon  a  normal  and  unrestricted 
diet  seems  to  me  to  more  than  compensate  for  the  neces- 
sarily approximative  estimates  of  the  quantities  of  nitrogen 
consumed. 

Proportions  of  Nitrogen  per  Hundred  Parts 

Article.  Nitrogen.  Authority. 

Beef . .  .  ]  f 

MuUon.  I  I  Payen,  p.  488.    This  is  the 

Chicken  !• 3.50  <]       approximative  estimate 

Turkey,   j  |       for  cooked  beef. 

Fish ...  J  I 

Eggs 1 .90         Payen,  p.  488. 

Beef-essence 0.87         O.  Loew  (actual  analysis). 

Head-cheese 2.24  "  " 

Milk 0.66         Payen,  p.  488. 

Custard 1.28         Average  of  milk  and  eggs. 

*  Payen,  "  Precis  theorique  et  pratique  des  substances  alimentaires,"  Paris, 

1865,  p.  48S  et  seq. 


388 


EXCRETION    OF    XITROGEX 


Authority. 
Average  of  milk  and  eggs. 

Payen,  p.  489. 


1.08        Payen,  p.  490. 


"     ;  Rice,  p.  180. 
O.  Loew  Tactual  analysis;. 


Pav 


en,  p.  490. 


Article.  Nitrogen. 

Ice-cream 1.28 

Cream-cakes 1.28 

Oysters 2.13 

Cheese 4. 1 2 

Bread  (includes  corn-cakes, 
cake,  crackers  and  bread- 
pudding  1 

Rice-pudding  (rice  and  custard)         1.18 

Oatmeal-gruel 0.086 

Potatoes 0.33 

Figs 0.92 

Butter 0.64 

Coffee o.  II 

Tea 0,02 

Tomatoes 

Cranberries 

Cauliflower 

Celer\- 

Lettuce 

Tomato-soup 

Tomato-catsup 

Grapes 

c^fon  These  anicles  contain  no  nitrogen  or  merely  a 

p'         ' ■  ■ trace  which  may  be  disregarded. 

Sweet  pickles 

Sugar 

Lemonade 

Molasses-and-water . 

"\'inegar 

Salt 

Pepper 

Bicarbonate  of  potash 

The  urine  of  each  twenty-four  hours  was  carefully  col- 
lected in  a  large  glass-stoppered  bottle  and  was  analyzed 
by  Mr.  Loew  by  the  following  methods: 

The  specific  gravity  was  always  determined  by  actual 
weight. 

The  urea  was  estimated  by  Liebig's  volumetric  process. 
In  this,  a  single  specimen  of  urine  was  used  for  estimating 
both  chloride  of  sodium  and  urea.  The  chloride  of  sodium 
was  determined  first,  and  afterward  the  urea  was  deter- 
mined with  a  different  mercurial  solution.  This  was  done 
to  avoid  confusion  and  possible  mistakes  in  the  readings 
of  the  burettes. 

The  uric  acid  was  determined  by  weight;  concentrating 
the  urine,  treating  it  for  twelve  hours  with  nitric  acid,  and 
collecting  the  cr^-stals  of  uric  acid. 


EXCRETION    OF    NITROGEN  389 

The  phosphoric  acid  was  determined  by  weight,  con- 
verting the  phosphates  into  j\l9HP04  +  7H2O. 

The  sulphuric  acid  was  determined  by  weight,  convert- 
ing the  sulphates  into  BaS04. 

The  examination  of  the  urinary  sediments  was  made 
by  myself  with  a  i  inch  objective,  allowing  the  specimen 
to  stand  for  about  twelve  hours. 

The  feces  were  passed  directly  into  clean  glass  vessels 
provided  with  air-tight  glass  covers,  and  weighed.  The 
nitrogen  of  the  feces  was  estimated  by  the  soda-lime  and 
platinum  process. 

PHYSIOLOGICAL    HISTORY    OF    WESTON    FOR    THE    FIFTEEN 
DAYS  DURING  WHICH   HE  WAS   UNDER   OBSERVATION 

The  fifteen  days  during  which  \\'eston  was  under  ob- 
servation were  divided  into  three  periods  of  five  days  each. 
During  the  first  period  of  five  days,  he  took  very  moderate 
exercise  and  assumed  to  be  "  training  "  for  the  walk,  though 
he  did  not  pursue  the  system  generally  adopted  in  training 
for  feats  of  endurance.  The  second  period  embraces  the 
five  days  of  the  walk.  The  third  period  of  five  days  after 
the  walk  was  one  of  almost  absolute  rest.  During  the 
entire  fifteen  days  he  abstained  altogether  from  alcoholic 
beverages.  Though  not  what  is  called  a  total  abstainer, 
Weston  is  not  an  habitual  drinker.  He  occasionally  takes 
a  glass  of  ale  or  wine,  but  this  is  rare.  During  the  first 
two  periods  Weston  did  not  smoke.  He  smoked  five  to 
seven  cigars  daily  during  the  third  period  of  five  days.  In 
the  records  of  food  taken,  the  time  of  eating  is  stated,  but 
I  have  not  thought  it  necessary  to  extend  the  tables  by 
giving  a  separate  account  of  each  meal  and  shall  generally 
give  in  a  single  table  the  entire  quantity  consumed  in  the 
twenty-four  hours. 

At  the  time  of  making  the  walk  Weston  was  thirty-one 
years  and  eight  months  old.  His  height  is  five  feet  and 
seven  inches.  His  ordinary  weight,  naked,  is  one  hundred 
and  twenty  to  one  hundred  and  twenty-five  pounds.  He 
has  never  had  any  serious  illness,  with  the  exception 
of  what  he  describes  as  vertigo  and  rather  serious  brain- 
symptoms  after  attempting  a  walk  when  he  was  suffering 
from  a  cold  and  headache.     This  occurred  in  the  summer 


390  EXCRETION   OF   NITROGEN 

of  1870.     He  does  not  know  that  he  has  any  hereditary- 
tendency  to  disease. 

His  general  build  is  slight  and  the  parts  above  the  waist 
are  very  light.  The  bones  of  the  chest  and  upper  extrem- 
ities are  small  and  the  muscles  are  but  little  developed. 
The  pelvis  is  unusually  broad  for  a  male,  and  the  lower 
extremities  are  so  formed  that  there  is  a  considerable  space 
between  the  thighs  from  the  knees  to  the  perineum.  The 
lower  extremities  are  remarkable  for  the  unusual  develop- 
ment of  the  muscles  that  move  the  thighs  upon  the  pelvis. 
In  walking,  it  is  observ^ed  that  Weston  makes  great  use  of 
these  muscles  and  uses  the  muscles  of  the  leg  very  little. 
The  calf  of  the  leg  is  small;  much  smaller  than  one  would 
expect  to  see  in  a  pedestrian. 

A  noticeable  peculiarity  about  the  muscles  of  the  thighs 
and  legs  is  that  they  never  become  very  hard.  They  were 
quite  soft  before  the  walk,  and  at  all  times  during  the  walk 
they  were  in  the  same  condition.  It  was  very  remarkable 
that  after  the  third  day  when  Weston  had  walked  within 
the  twenty-four  hours  ninety-two  miles,  the  muscles  were 
as  soft  as  ever.  It  has  seemed  to  me  that  this  peculiarity 
of  the  muscles  is  advantageous.  When  the  muscles  are" 
very  hard  from  thorough  training,  prolonged  exertion  is 
likely  to  produce  cramps,  due,  perhaps,  to  exaggeration 
of  the  normal  muscular  irritability.  This  is  a  difficulty  ex- 
perienced by  pedestrians.  In  the  case  of  Weston,  the 
movements  were  always  free,  and,  according  to  his  state- 
ments, he  w^as  never  much  fatigued.  Only  once  during 
the  five  days  of  the  walk  did  he  say  that  he  was  "  leg- 
weary."  What  he  complained  of  most  was  want  of  sleep, 
and  at  one  time,  vertigo.  The  conformation  of  the  feet 
is  perfect;  the  toes  are  straight,  the  instep  is  high,  and  the 
heel  is  very  long,  giving  a  remarkable  leverage  for  the 
tendo  Achillis.  The  heel  does  not  project,  as  in  the  negro, 
but  the  tendo  Achillis  passes  straight  to  the  calf  of  the  leg. 

The  nervous  element  seemed  to  me  very  important  in 
the  tasks  accomplished  by  Weston.  On  the  fourth  day  of 
the  w^alk,  having  made  on  the  first  day,  eighty  miles,  on 
the  second,  forty-eight  miles,  and  on  the  third,  ninety-two 
miles,  he  kept  on  the  track  after  having  w^alked  more  than 
fifty  miles,  until  vertigo  became  so  great  that  he  could  not 
see  to  turn  the  corners.     He  was  forced  to  abandon  hope 


EXCRETION    OF    NITROGEN  391 

of  making  four  hundred  miles  in  five  days;  but  on  the  fifth 
day,  he  appeared  again  at  10  a.  m.,  and  walked  more  than 
forty  miles. 

FIRST    PERIOD,    FIVE    DAYS    BEFORE    THE    WALK 

At  midnight,  November  15,  1870,  the  observations 
were  begun.  At  forty  minutes  past  twelve  his  general 
condition  was  as  follows: 

Weight  (naked) 120.5  lbs.  (54  k.  655  grammes.) 

Temperature  under  the  tongue 98.6°  (37°  C). 

Pulse  (sitting  and  perfectly  tranquil) 64. 

Respirations 19. 

Immediately  after  this  examination  Weston  went  to 
bed. 

NOVEMBER    1 6,    FIRST    DAY 

Weston  slept  well  during  the  night  and  rose  in  good 
health  and  spirits  at  8.15  a.  m.  He  felt  well  the  entire  day; 
took  his  breakfast  at  9.15  a.  m.;  dinner  at  i.io  p.  m.;  and 
supper  at  7.55  p.  m.  He  walked  during  the  day  about 
fifteen  miles.  Though  feeling  well  he  was  worried  and 
anxious  about  the  business  arrangements  for  his  walk.  He 
did  not  go  to  bed  until  2.35  a.  m.,  November  17.  He 
slept,  during  the  twenty-four  hours,  seven  hours  and  thirty 
minutes. 

Weights  and  Analyses  of  Food  and  Drink  for  the  Twenty- 
four  Hours 

Oz.  Av.  Nitrogen,  in  grains. 

Beefsteak 12.25  187.58 

Mutton-chops 3.00  45-94 

Eggs 2.76  22.94 

Milk...    7.21  20.82 

Bread 9.88  47.48 

Potatoes 8.25  11-99 

Butter 2. 1 2  5.94 

Sugar 1.78  00.00 

Coffee 3560  17-13 

Tea 16.03  1.40 

Water 24.00  00.00 

Salt 0.09  00.00 

Pepper 0.02  00.00 

122.99  361.22 

(3,492.17  grammes.)   (23.404  grammes.) 

Total  ingesta (7  lbs.,  10  jS^  oz.) 

Liquids (5  lbs.,    2-^%^  oz.) 


392  EXCRETION    OF    NITROGEN 

Analyses  of  Excretions  of  Twenty-four  Hours 

URINE 

Quantity 39.55  fl  §    (1,170.0  cc.) 

Specific  gravity 1024  o 

Urea 650.08  grains,  42. 1 20  grammes. 

Nitrogen  in  urea 303.37      "        19.656         " 

Uric  acid 3.55       "  0.230         " 

Phosphoric  acid 51.46      "  3-334         " 

Sulphuric  acid 38.37      "  2.486 

Chloride  of  sodium 195.02      "        12.636         " 

This  urine  presented  a  light  flocculent  sediment,  which  contained  a 
large  number  of  octahedra  of  oxalate  of  lime. 

FECES 

Quantity 3.70  oz.  av.     105.0      grammes. 

Nitrogen 1 9.89  grains,         i  .289 

Nitrogen  in  urea  and  feces  combined . .    323.26      "  20.945         " 

Nitrogen  of  urea  and  feces  per  100  parts  of  nitrogen  of  food .  .   89.49  parts. 

Uric  acid  per  100  parts  of  urea 0-538     " 

I  Weight  (naked) 120.5  lbs.  (54  k.  655  grammes.) 

J  Temperature  under  the  tongue 997°  (37°  C.) 

I  Pul.se,  full  and  soft 75. 

(  Respirations 20. 


10.30  P.  M. 


NOVEMBER    1 7,    SECOND    DAY 

After  going  to  bed  at  2.35  a.  m.,  Weston  rose  at  8.45 
A.  M.  He  had  a  little  headache  in  the  middle  of  the  day. 
He  took  breakfast  at  9.40  a.  m.;  dinner  at  2.30  p.  m.;  and 
supper  at  7.40  p.  m.  He  walked  during  the  day  about 
five  miles.  He  went  to  bed  at  11.30  p.m.  He  slept, 
during  the  twenty-four  hours,  six  hours  and  forty  minutes. 

Weights  and  Analyses  of  Food  and  Drink  for  the  Twenty- 
four  Hours 


Oz.  Av. 

Nitrogen,  in  grains. 

Beefsteak 

525 

80.39 

Roast  beef 

5-25 

4.14 

80.39 
3441 

Eggs 

Milk   

463 

13-37 

Bread 

8.50 

40.16 

Potatoes 

10.00 

14.44 

Tomatoes  (stewed) .  .  . 

7.00 

00.00 

Butter 

2.95 

8.26 

Sugar 

1.25 

00.00 

Coffee 

32.32 

15-53 

Tea 

16.03 

1.40 

Water 

8.00 

00.00 

Salt 

0.02 

00.00 

Pepper 

0.09 

00.00 

105.43  (2,987. 92 gms.)    288.35  (18.682  gms.) 
Total  ingesta  (6  lbs.,  9iVo  o^.).     Liquids  (3  lbs.,  12-^^  oz.). 


EXCRETION    OF    NITROGEN  393 

Analyses  of  Excretions  of  Twenty-four  Hours 

URINE 

Quantity 38.0303    (1,125.000.) 

Specific  gravity 1024.4 

Urea 590-35  grains,  38.250  grammes. 

Nitrogen  in  urea 275.50      "        16.517 

Uric  acid 4.03      "          0.261 

Phosphoric  acid 44.o8      "          2.921 

Sulphuric  acid 40.92      "          2.651 

Chloride  of  sodium 1 58.00      "         10.237 

The  sediment  was  the  same  as  on  November  16,  but  the  octahedra 
of  oxalate  of  lime  were  more  abundant. 

FECES 

Quantity 4.78  oz.  av.     135.5      grammes. 

Nitrogen 25.68  grains,         i  .664 

Nitrogen  in  urea  and  feces  combined . .    301.18      "  18. 181         " 

Nitrogen  of  urea  and  feces  per  100  parts  of  nitrogen  of  food .    104.45    parts. 

Uric  acid  per  100  parts  of  urea 0.683 

r  Weight  (naked) 121.25  Ibs^  (55  kilos.) 

I  Temperature  under  the  tongue 98.4°  (36.9"  C.) 

j  Pulse    73. 

[  Respirations 20. 


11.20  p.  M. 


NOVEMBER    1 8,    THIRD    DAY 

Weston  rose  at  9  a.  m.;  took  his  breakfast  at  9.50  a.  m.; 
dinner  at  2.15  p.m.;  and  supper  at  7.35  p.m.  He  said 
he  felt  '*  splendid  "  all  day.  He  wrote  about  seven  hours 
and  \valked  about  live  miles.  He  ^vas  very  cheerful  all 
day  and  went  to  bed  at  12.20  a.  m.,  November  19.  He 
slept,  during  the  twenty-four  hours,  nine  hours. 

Weights  and  Analyses  of  Food  and  Drink  for  the  Twexty- 

FOUR  Hours 

Beefsteak 

Eggs 

Milk 

Bread 

Potatoes 

Butter 

Sugar 

Coffee 

Tea 

Salt 

Pepper 


Oz.  Av. 

Nitrogen,  in  grains 

10.37 

158.79 

2.76 

22.94 

7.21 

20.82 

7-75 

36.62 

5-13 

7-41 

3-13 

8.76 

1-75 

00.00 

32.32 

15-53 

16.03 

1.40 

0.09 

00.00 

0.02 

00.00 

86.56  272.27 

(2,453.67  grammes.)    (17.641  grammes.) 

Total  ingesta (5  lbs.,  6.r^  o^-^ 

Liquids (3  lbs.,  7^  oz.) 

26 


394  EXCRETION    OF    NITROGEN 

Analyses  of  Excretions  of  Twenty-four  Hours 

URINE 

Quantity 46.15  fl  |   (1,365.0  cc.) 

Specific  gravity 1023.  i 

Urea 653.08  grains,  42.315  grammes. 

Nitrogen  in  urea 30477      "        ^9-747 

Uric  acid 0.94      "  0.061         " 

Phosphoric  acid 45- H      "  2.925 

Sulphuric  acid 38.86      "  2.518         " 

Chloride  of  sodium 191.70      "        12.421 

Tbere  was  a  rather  light  cloudy  sediment  which  contained  a  little 
mucus  and  a  very  few  small  octahedra  of  o.xalate  of  lime. 

FECES 

Quantity 476  oz.  av.     135.0      grammes. 

Nitrogen 25.59  grains,         1.658 

Nitrogen  in  urea  and  feces  combined. .   330.36      "  21.405 

Nitrogen  of  urea  and  feces  per  100  parts  of  nitrogen  of  food.    121.30   parts. 

Uric  acid  per  100  parts  of  urea o.  144     " 

I   Weight  (naked) 120  lbs.  (54  k.  432  grammes.) 

I  Temperature  under  the  tongue 98°  (36.7°  C.) 

11.55  P.M.        j  p^jgg ^j 

[  Respirations.    20. 

NOVEMBER    IQ,    FOURTH    DAY 

Weston  rose  at  8.35  a.  m.,  feeling  as  well  as  possible; 
took  breakfast  at  9  a.  m.  ;  dinner  at  4.45  p.  m.  ;  and  supper  at 
10.45  P-  ^^-  He  said  he  felt  "  splendid  "  all  day.  He  walked 
during  the  day  about  fifteen  miles,  was  very  cheerful  and 
went  to  bed  at  12.45  ^-  M-»  November  20.  He  slept,  dur- 
ing the  twenty-four  hours,  seven  hours  and  fifteen  minutes. 

Weights  and  Analyses  of  Food  and  Drink  for  the  24  Hours 

Oz.  Av.  Nitrogen,  in  grains. 

Beefsteak 4.25  65.08 

Mutton-chops   4.88  74-72 

Roast  beef    4.88  74  72 

Eggs 4.14  34.41 

Milk 4.38  12.65 

Bread 10.25  48-43 

Potatoes 0.88  1.27 

Butter 2.43  6.80 

Sugar 1. 6 1  00.00 

Coffee 32.32  15.53 

Tea 16.03  I  -4° 

Salt 0.09  00.00 

Pepper ....  0.05  00.00 


86.19  335°^ 

(2,443.19  grammes.)    (21.706  grammes.) 
Total  ingesta  (5  lbs.,  6^^^  02. ).     Liquids  (4  lbs.,  4j^  oz.). 


EXCRETION    OF    NITROGEN  395 

Analyses  of  Excretions  of  Twenty-four  Hours 

URINE 

Quantity 3245  fl  §  (960.0  cc.) 

Specific  gravity 1027.6 

Urea 607.55  grains,  39.365  grammes. 

Nitrogen  in  urea 283.52      "         18.370 

Uric  acid i  .06      "  0.069        " 

Phosphoric  acid 67.00      "  4.341 

Sulphuric  acid. .        51.50      "  3-337         " 

Chloride  of  sodium 106.68      "  6.912         " 

This  urine  presented  a  copious  fawn-colored  sediment  which  cleared 
up  with  gentle  heat.  It  contained  the  amorphous  urates  with  a  large 
number  of  octahedra  of  the  oxalate  of  lime. 

FECES 

Quantity 3.17  oz.  av.     90.0      grammes. 

Nitrogen 17.05  grains,       1.105 

Nitrogen  in  urea  and  feces  combined..    300.57      "           19-475         " 
Nitrogen  of  urea  and  feces  per  100  parts  of  nitrogen  of  food.   89.75    parts. 
Uric  acid  per  100  parts  of  urea o.  1 74     " 

Weight  (naked),  taken  at  12.35  A.M.,  November  20,  118.5  (53  k.  745 
grammes). 

C  Temperature  under  the  tongue 99- 1°  (37-3°  C.) 

11.55  P.M.       <  Pulse 78. 

(  Respirations 23. 

NOVEMBER    20,    FIFTH    DAY 

Weston  rose  at  10.45  ^-  ^i-'  feeling  remarkably  well. 
He  took  breakfast  at  11.30  a.  m.;  dinner  at  5.55  p.  m.;  and 
supper  at  11. 15  p.  m.  He  said  he  felt  "  splendid  "  all  day. 
He  walked  about  one  mile  during  the  day.  He  started 
on  his  walk  at  12.15  a.  m.,  November  21.  He  slept,  during 
the  twenty-four  hours,  ten  hours. 

Weights  ani?  Analyses  of  Food  and  Drink  for  the  24  Hours 

Oz.  Av.  Nitrogen,  in  grains. 

Beefsteak 18.25  279.45 

Eggs 6.90  57-35 

Milk 11.33  32-71 

Bread 8.88  41-96 

Potatoes 3.00  4.43 

Butter 2.75  7.70 

Sugar 1.75  00.00 

Coffee 32.32  15-53 

Tea    16.03  I -40 

Salt 0.08  00  00 

Pepper 0.05  00.00 

101.34  440-43 

(2,872.63  grammes.)    (28.536  grammes.) 

Total  ingesta  (6  lbs.,  St^  o^.).     Liquids  (3  lbs.,  i  i-/o\  o^.). 


396  EXCRETION   OF    NITROGEN 

Analyses  of  Excretions  of  Twenty-four  Hours 

URINE 

Quantity 34-00  fl  |   (1.050.0  cc.) 

Specific  gravity 1025.2. 

Urea 640.13  grains,  41-475  grammes. 

Nitrogen  in  urea 298.73      "         19.355 

Uric  acid 1-73      "  0-ii2 

Phosphoric  acid 43-Oi       "  2.787 

Sulphuric  acid 38-18      "  2.474 

Chloride  of  sodium 145-^5      "  9-450 

This  specimen  of  urine  presented  rather  a  faint  cloudy  sediment 
which  contained  a  large  number  of  octahedra  of  the  oxalate  of  lime. 

FECES 

Quantity 3-97  oz.  av.     1 1 2.5      grammes. 

Nitrogen 21.33  grains,         1.382 

Nitrogen  in  urea  and  feces  combined. .   320.06      "  20.737         " 

Nitrogen  of  urea  and  feces  per  100  parts  of  nitrogen  of  food.  72.67   parts. 
Uric  acid  per  100  parts  of  urea 0.270     " 

f  Weight  (naked) 1 19.2  lbs.  (54  k.  62  grammes.) 

J  Temperature  under  the  tongue 99-5°  (37-5°Q 

1 1.45  P.  M.        I  p^jgg ^^ 

[  Respirations 25. 

SECOND    PERIOD,    FIVE    DAYS    OF    THE    WALK 

The  walk  took  place  in  a  large  building  of  corrugated 
iron,  known  as  the  "  Empire  Skating  Rink,"  on  Third 
Avenue,  near  Sixty-fourth  Street.  This  building  is  ob- 
long, measuring  170  by  350  feet.  A  track  made  of  boards 
covered  with  dirt  and  fine  shavings  was  laid  out  in  the 
form  of  a  parallelogram.  This  track  was  measured  by 
Mr.  Joseph  L.  T.  Smith,  surveyor,  in  the  presence  of  Prof. 
Doremus  and  myself.  The  circuit,  taken  two  and  a  half 
feet  from  the  inside,  measured  735to*o"  feet.  This  measure- 
ment was  made  with  a  metallic  tape,  adjusted  for  tempera- 
ture and  tested  in  our  presence.  In  making  the  measure- 
ment. Prof.  Doremus  was  at  one  end  of  the  tape  and  I 
was  at  the  other,  and  every  reading  was  carefully  verified. 
Seven  full  circuits  and  i29TTnr  additional  feet  made  a  full 
mile.  In  computing  the  walk  the  distance  was  noted  by 
circuits.  Three  judges  were  in  attendance  day  and  night; 
one  calling  the  time  of  each  circuit,  and  two  checking  off 
the  circuits  in  a  book  provided  for  that  purpose.  In  addi- 
tion, either  Prof.  Doremus,  Prof.  Mott  or  I  was  con- 
stantly present.     Weston  had  retiring-rooms  in  the  front 


EXCRETION   OF   NITROGEN  397 

of  the  building,  where  his  food  was  prepared,  where  he 
slept  and  where  our  observations  were  taken.  The  dis- 
tance from  the  judges'  stand  to  the  door  of  these  rooms 
was  I45tVo   feet. 

During  the  walk  Weston  took  but  few  regular  meals, 
a  great  part  of  his  nourishment  being  taken  while  actually 
walking.  In  this  way  he  took  beef-essence,  soft-boiled 
eggs,  gruel,  tea,  cofifee  and  all  other  drinks.  I  shall  not, 
therefore,  give  the  time  of  the  meals  taken  during  this 
period,  but  simply  state  the  entire  quantity  consumed  in 
each  twenty-four  hours. 

In  regard  to  the  distance  walked,  we  are  all  satisfied 
that  there  is  no  room  for  doubt.  But  although  the  task 
proposed  was  not  accomplished,  the  effort  was  so  great, 
that  I  have  thought  it  best  to  give  the  history  of  these  five 
days  rather  fully  in  detail. 

NOVEMBER    21,     FIRST    DAY 

The  following  is  a  summary  of  the  twenty-four  hours 
of  November  21 : 

12  00  to    12  15  A.  M.     15  minutes'  rest  before  starting. 
12  15    to     49     "         3  h.  54  m.  wall<ing  20  miles,  with  4  stops  for  uri- 
nation, averaging  24  sec.  eacli. 

4  9   to     7  58     "         3  h.  and  49  m.  rest  (sleep). 

7  58   to     9    6     "         I  h.  and  8  m.  walking  5f  miles. 
9    6   to     919     "         13  m.  for  breakfast. 

9  19  A.  M.  to  I  P.  M.  3  h.  and  41  m.  walking  17  miles,  with  5  m.  12  sec. 
for  defecation,  and  2  stops  for  urination,  aver- 
aging 30  sec.  each. 

I  00   to      I  46     "         46  m.  for  dinner. 

I  46  to  325  "  I  h.  and  39  m.  walking  8  miles,  with  2  stops  for 
urination,  averaging  27^  sec.  each. 

3  25   to      3  32     "         7  minutes'  rest,  sitting  on  the  track. 

3  32  to  5  34  "  2  h.  and  2  m.  walking  9^  miles,  with  2  stops  for 
urination,  averaging  26J  sec.  each. 

5  34   to      6  27     "         53  minutes'  rest  (supper). 

6  27    to     8  38     "         2  h.  and  11  m.  walking  12  miles,  with  3  stops  for 

urination,  averaging  26  sec.  each. 

8  38    to      8  48     "  10  minutes'  rest,  sitting  on  the  track. 

8  48   to    10  32^  "         I  h.  444  m.  walking  8  miles,  with  2  stops  for  uri- 
nation, averaging  32|-  sec.  each. 
i0  32|-to    1200     "         I  h.  274  minutes'  rest,  continued  into  November 
22,  4'h.  58  m. 

During  the  24  hours  of  November  21,  Weston  walked  80  miles  in 
16  h.  and  20  m.,  including  5  m.  12  sec.  for  defecation  and  6  m.  45  sec.  for 
urination.  Deducting  the  time  for  defecation  and  urination,  his  walking- 
time  was  16  h.  8  m.  and  3  sec,  and  he  averaged  a  fraction  less  than  5 


398  EXCRETION    OF    NITROGEN 

miles  per  hour.  He  had  17  minutes'  rest,  sitting  by  the  traci<,  and  7  h. 
and  23  m.  for  breakfast,  dinner,  supper  and  sleep.  He  urinated  15  times 
on  the  track.  He  vomited  a  little  liquid  twice  during  the  night  at  10.50 
and  1 1. 15.     He  slept,  during  the  twenty-four  hours,  about  i  hour. 

Walking  80  miles..  .  .    16  h. 

Defecation 

Urination 

Rest  on  the  track. . . . 
Rest  off  the  track 7  h. 


8  m. 

3  sec. 

5  " 

12    " 

6  " 

45    " 

17  " 

23  " 

23  h.       59  m.       60  sec.  =  24  hours. 

During  the  whole  of  the  first  day,  Weston  seemed  to  feel  very  well 
and  made  his  walk  with  ease.  He  was  slightly  nauseated  at  times,  but  he 
said  that  he  had  always  more  or  less  disturbance  of  that  kind  when  he 
first  began  a  walk. 

Weights  and  Analyses  of  Food  and  Drink  for  the  Twenty- 
four  Hours 

Oz.  Av.  Nitrogen,  in  grains. 

Mutton-chops 2.00  30.62 

Eggs 6.90  57.35 

Milk 5.66  16.34 

Bread 1.25  5.91 

Butter 2.63  7.36 

Sugar 1 .63  00.00 

Coffee 67.67  32.57 

Tea 16.03  1.40 

Water 6.75   _  00.00 

Lemonade 71.16  00.00 

Molasses-and-water  ..  4.40  00.00 

Salt 0.08  00.00 

Pepper 0.05  00.00 

Bicarbonate  of  potash .  0.04  00.00 

186.25  151-55 

(5,282.38  grammes.)     (9.820  grammes.) 

Total  ingesta (11  lbs.,  lOyVo  oz.) 

Liquids (10  lbs.,  i  lyVo  oz.) 

Analyses  of  Excretions  of  Twenty-four  Hours 

URINE 

Quantity 42.09  fl  ^  (1,245.0  cc.) 

Specific  gravity 1028.6 

Urea 710.00  grains,  46.065  grammes. 

Nitrogen  in  urea 331-33      "  21.497 

Uric  acid 0.32      "  0.02 1 

Phosphoric  acid 84.95      "  5- 5^4 

Sulphuric  acid 73-39      "  4755 

Chloride  of  sodium 96.00      "  6.220 

This  specimen  of  urine  presented  rather  a  faint  cloudy  sediment  which 
contained  a  large  number  of  octahedra  of  the  oxalate  of  lime. 


EXCRETION    OF   NITROGEN  399 

FECES 

Quantity 4-8o  oz.  av.     136.0      grammes. 

Nitrogen 25.77  grains,         1.670 

Nitrogen  in  urea  and  feces  combined. .   357-io      "  22.167 

Nitrogen  of  urea  and  feces  per  100  parts  of  nitrogen  of  food .    235.63   parts. 

Uric  acid  per  100  parts  of  urea 0.045    " 

r  Weight  (naked) 1 16.5  lbs.  (52  k.  838  grammes.) 

Temperature  under  the  tongue 95.3°  (35-3°  C.) 

10.40P.M.       \  p^i^^t; 98. 

(^  Respirations    20. 

NOVEMBER    22,    SECOND    DAY 

The  following  is  a  summary  of  the  twenty-four  hours 
of  Xovember  22: 

12  00   to     4  58  A.  M.     4  h.  and   58  m.  rest,  continued  from  November 
21,  before  starting,  making,  during  the  night  of 
the  2ist  and  22d,  6  h.  and  25^^  m. 
4  58   to     6  58     "         2  h.  walking  8f  miles,  with  i  stop  of  6  m.  for  defe- 
cation. 
10  m.  rest,  sitting  on  the  track. 
25  m.  walking  i-f-  miles. 

1  h.  and  32  m.  rest  (breakfast). 

2  h.  and  7  m.  walking  9*  miles,  with  2  stops  for 
urination,  averaging  32  sec.  each. 

15  m.  rest,  sitting  on  the  track. 

2  h.  and  14  m.  walking  10  miles,  with  2  m.  rest 
and  2  stops  for  urination,  averaging  29  sec.  each. 

14  m.  rest,  sitting  on  the  track. 

2  h.  and  10  m.  walking  10  miles,  with   i  stop  for 
urination,  of  25  sec. 
4    5    to    10  24     "         6  h.    19  m.     Stopped  for  sleep  but  dozed  only. 

Ate  supper  before  starting  again. 
10  24  to   I2,less49sec.  Walking  8  miles  in  i  h.  36  m.  less  49  sec.  on  his 
walk  of  112  miles  in  24  h.  and  continued  walk- 
ing into  November  23. 

During  the  24  hours  of  November  22,  Weston  walked  48  miles  in 
10  h.  and  32  m.,  including  6  m.  for  defecation  and  2  m.  27  sec.  for  urina- 
tion. Deducting  the  time  for  defecation  and  urination,  his  walking-time 
was  10  h.  23  m.  and  33  sec,  and  he  averaged  about  4.62  miles  per  hour. 
He  had  39  minutes'  rest,  sitting  on  the  track,  and  12  h.  and  49  m.  for 
breakfast,  dinner,  supper  and  sleep.  He  urinated  5  times  on  the  track. 
When  he  stopped  at  4.05  p.  M.  he  was  undressed,  wrapped  in  a  long  red- 
fiannel  gown  and  a  blanket,  carried  to  a  vehicle  and  driven  about  five 
blocks  to  a  private  house  to  sleep.  He  says  that  he  did  not  sleep,  but 
dozed  and  got  no  rest.  About  9  30  P.  M.  he  was  brought  back  to  the  rink 
in  the  way  he  was  taken  out,  ate  supper  and  began  at  10.24  P.M.  his 
first  attempt  to  walk  one  hundred  and  twelve  miles  in  twenty-four  con- 
secutive hours.  He  slept,  during  the  twenty-four  hours,  4  hours  and  28 
minutes. 


6  58 

to 

7  8  " 

7  8 

to 

7  33  " 

7  33 

to 

9  5  " 

9  5 

to 

II  12  " 

II  12 

to 

II  27  " 

II  27 

to 

I  41  P.  M, 

I  41 

to 

I  55   " 

I  55 

to 

4  5  " 

400                      EXCRETION    OF  NITROGEN 

Walkinj^  48  miles. .    10  h.  23  m.         33  sec. 

Defecation 6  " 

Urination 2  "           27    " 

Rest  on  tlie  track..  39  " 

Rest  off  the  track..    12  "  49  " 


22  h.       119  m.         60  sec.  =  24  hours. 


Weights  and  Analyses  of  Food  and  Drink  for  the  Twenty- 
four  Hours 

Oz.  Av.  Nitrogen,  in  grains. 

Roast  beef 4.00  61.25 

Chicken 2.25  34.45 

Eggs 8.28  68.82 

Milk 5.66  16.34 

Bread 10.50  49.61 

Potatoes 2.00  2.89 

Butter 0.50  1.40 

Sugar 1.75  00.00 

Coffee 57.82  27.83 

Tea 38.08  3.33 

Lemonade 34-84  00.00 

Salt 0.08  00.00 

Pepper 0.05  00.00 

165.81  265.92 
(4,700.13  grammes.)    (17,229  grammes.) 

Total  ingesta (10  lbs.,  Stoo  oz-) 

Liquids (8  lbs.,  S^%%  oz.) 


Analyses  of  Excretions  of  Twenty-four  Hours 


Quantity 33-50  fl  |  (99i-0  cc.) 

Specific  gravity 1030.0. 

Urea 702.86  grains,  45.540  grammes. 

Nitrogen  in  urea 328.00      "        21.252 

Uric  acid 0.14      "          0.009 

Phosphoric  acid 72.14      "          4-674 

Sulphuric  acid 56.90      "          3.687 

Chloride  of  sodium 91.68      "          5.940 

This  specimen  of  urine  presented  rather  a  faint,   cloudy  sediment, 
which  contained  a  large  number  of  octahedra  of  the  oxalate  of  lime. 

FECES 

Quantity 7.94  oz.  av.     225.0      grammes. 

Nitrogen 42-64  grains,        2.763 

Nitrogen  in  urea  and  feces  combined. .   370.64      "  24.015         " 

Nitrogen  of  urea  and  feces  per  100  parts  of  nitrogen  of  food.    139.39  parts. 
Uric  acid  per  100  parts  of  urea 0.020 


lO  p.  M. 


EXCRETION    OF    NITROGEN  401 

r  Weight  (naked) 1 16.25  lbs.  (52  k.  724  grammes.) 

j  Temperature  under  the  tongue 94-8°  (34.9°  C.) 

1  Pulse 93. 

1^  Respirations 23. 


NOVEMBER    23,    THIRD    DAY 

The  following  is  a  summary  of  the  twenty-four  hours 
of  November  23: 

12  00   to     6    6  a.  M.     6  h.  and  6  m.  walking  27^  miles,  with  one  stop  of 
4  m.  30  sec.  for  rest,  and  4  stops  for  urination, 
averaging  30^  sec.  each. 
8  minutes'  rest,  sitting  on  the  track. 
M.      7  h.  and  17  m.  walking  33  miles,  with  4  stops  for 
urination,  averaging  31^  sec.  each. 

6  minutes'  rest,  sitting  on  the  track. 
47  m.  walking  3f  miles,  with  one  stop  of  34  sec. 

for  urination. 

7  minutes'  rest,  sitting  on  the  track. 
34  m.  walking  2J  miles. 
27  minutes'  rest,  sitting  on  the  track. 
I  h.  14  m.  walking  5J  miles,  including  2  stops  for 

urination,  averaging  2yl  sec.  each. 
30  minutes'  rest,  sitting  on  the  track. 
30  m.  walking  2  miles,  with  one  stop  of  58  sec. 

for  urination. 

1  h.  and  3  m.  rest  in  his  room  (supper). 

2  h.  and  22  m.  walking  11  miles,  with  one  stop  of 
30  sec.  for  urination. 

10  minutes'  rest,  sitting  on  the  track. 

I  h.  and  31   m.  walking  7  miles,  with  one  stop  of 

43  sec.  for  urination. 
I  h.  and  8  m.  rest,  continued  into  November  24. 

During  the  24  hours  of  November  23,  Weston  walked  92  miles  in 
20  h.  and  21  m.,  including  4  m.  30  sec.  rest,  and  7  m.  47  sec.  for  urina- 
tion. His  walking-time  was  20  h.  8  m.  and  43  sec.  and  he  averaged  a 
fraction  more  than  4J  miles  per  hour.  He  had  i  h.  32  m.  and  30  sec. 
rest,  sitting  on  the  track,  and  2  h.  and  11  m.  rest  in  his  room.  Before  12, 
midnight,  November  22,  he  had  walked  8  miles  in  i  h.  35  m.  and  11  sec, 
making  100  miles  in  24  h.  and  28  m.  His  last  rest  of  i  h.  and  8  m.  was 
continued  into  November  24  i  h.  and  33  m.  He  urinated  on  the  track 
14  times. 

During  the  early  part  of  the  day,  Weston  seemed  cheerful  and  con- 
fident, but  after  walking  about  sixty  miles,  he  complained  of  drowsiness 
and  found  it  absolutely  impossible  to  make  the  time  necessary  to  accom- 
plish his  hundred  and  twelve  miles  in  twenty-four  consecutive  hours.  He 
stated  that  he  was  not  fatigued,  but  suffered  only  from  want  of  sleep.  He 
was  not  much  depressed  at  his  first  failure,  as  he  intended  to  make  a  sec- 
ond trial  of  the  hundred-and-twelve-mile  walk. 

He  began,  10.24  P-  M->  November  22,  his  first  attempt  to  make  112 
miles  in  24  consecutive  hours.     He  failed  on  account  of  want  of  sleep. 


6    6 

to 

614  " 

614 

to 

I  31  p. 

I  31 
I  37 

to 
to 

1  37     " 

2  24     " 

2  24 
231 

3  5 

332 

to 
to 
to 

to 

2  31     " 

3  5     " 
3  32     " 
446     " 

446 
516 

to 
to 

516     " 
5  46     " 

546 
649 

to 
to 

649     " 
9  II     " 

9  II 
921 

to 
to 

921     " 

10  52     " 

0  =;2 

to 

I  2  00  M. 

40  2 


EXCRETION    OF    NITROGEN 


not  having  slept  well  the  six  hours   before  the  attempt.      He   had  no 

passage  from  his  bowels  during  these  24  hours.     He  slept,  during  the 
24  hours,  30  minutes. 

Walking  92  miles 20  h.       8  m.     43  sec. 

Urination  . .  .  .* 7  "      47    " 

Rest  on  the  track i  "      32  "      30   " 

Rest  off  the  track 2  "       11" 


23  h.     58  m.   1 20  sec.  =  24  hours. 


Weights  and  Analyses  of  Food  and  Drink  for  the  Twenty- 
four  Hours 

Oz.  Av.  Nitrogen,  in  grains. 

Beef-essence 22.26  84.73 

Eggs 8.28  68.82 

Milk 6.18  17.84 

Bread 1.50  709 

Oatmeal-gruel 6.78  2.55 

Butter 0.50  1.40 

Sugar 2.00  00.00 

Coffee 95.95  46.18 

Lemonade 27.56  00.00 

Salt 0.08  00.00 

Pepper 0.05  00.00 

171. 14  228.61 

(4,851.22  grammes.)    (14.812  grammes.) 

Total  ingesta (10  lbs.,  i  lyVo  oz.) 

Liquids (9  lbs.,  I4tVo  oz-) 


Analyses  of  Excretions  of  Twenty-four  Hours 


Quantity 40.56  fl  3   (1,200.0  cc.) 

Specific  gravity 1032 .  5. 

Urea 851 .95  grains,  55.200  grammes. 

Nitrogen  in  urea 397-58      "        25.760 

Uric  acid 4. 74      "  o. 307 

Phosphoric  acid 102.25      "  6.625 

Sulphuric  acid    63.71       "  4.128 

Chloride  of  sodium 44.45      "  2.880 

This  specimen  presented  a  whitish,  flocculent  and  rather  copious  sedi- 
ment which  contained  a  large  number  of  octahedra  of  the  oxalate  of  lime. 


NO    FECES    PASSED 


Nitrogen  of  urea  (no  feces)  per  100  parts  of  nitrogen  of  food  173.91    parts. 
Uric  acid  per  100  parts  of  urea 0.566      " 


EXCRETION    OF    NITROGEN  403 

f  Weight  inaccurately  taken 

J  Temperature  under  the  tongue 96.6'  (35.9'  C.) 

11.15P.  M.       1  Pulse  (76  at  5  P.  M.) 109. 

Respirations 22 . 


I 


NOVEMBER  24,  FOURTH  DAY 


The  following  is  a  summary  of  the  twenty-four  hours 
of  November  24: 

12  00   to      I  33  A.  M.     I  h.  33  m,  rest  in  room,  continued  from  November 
23,  making  in  all,  2  h.  41  m.  rest  for  the  night 
of  November  23  and  24. 
I  33    to     412     "         2  h.  39  m.  walking  10  miles,  with  3  m.  stop  for 
defecation  and  30  sec.  for  urination. 
5  h.  and  47  m.  rest  in  room. 

4  h.  59  m.  walking  23!^  miles,  with  3  stops  for  uri- 
nation, averaging  30I  sec.  each. 

5  minutes'  rest,  sitting  on  the  track. 
3  h.  and  7  m.  walking  I4f  miles,  with  2  stops  for 

urination,  averaging  42^  sec.  each. 
3  minutes'  rest,  sitting  on  the  track. 

16  m.  walking  i4  miles,  with  30  sec.  for  urination. 
10  minutes'  rest,  sitting  on  the  track. 
12  m.  walking  i  mile. 
12  minutes'  rest  in  his  room. 

7  m.  walking  f  of  a  mile. 
56  minutes'  rest  in  his  room. 

10  m.  walking  f  of  a  mile,  with  40  sec.  for  urina- 
tion. 

5  minutes'  rest,  sitting  on  the  track. 
33  m.  walking  24-  miles. 

8  minutes'  rest,  sitting  on  the  track. 
19  m.  walking  li  miles. 
10  minutes'  rest,  sitting  on  the  track. 

17  m.  walking  i  mile,  with  50  sec.  for  urination. 
33  minutes'  rest  in  room. 

9  m.  walking  f  of  a  mile. 

I  h.  and  30  m.  rest  in  room,  continued  into  Novem- 
ber 25. 

During  the  24  hours  of  November  24.  Weston  walked  57  miles  in  1 2 
h.  and  48  m.,  including  3  m.  for  defecation,  and  5  m.  and  26  sec.  for  uri- 
nation. His  walking-time  was  12  h.  39  m.  and  34  sec,  averaging  almost 
exactly  4^  miles  per  hour.  He  had  41  m.  rest,  sitting  on  the  track,  and  10 
h.  and  31  m.  rest  in  his  room.  He  urinated  on  the  track  10  times.  His 
last  rest,  i  h.  and  30  m.,  was  continued  into  November  25,  for  9  h.  56  m., 
making,  during  the  night  of  November  24  and  25,  11  h.  26  m.  rest. 

He  began,  at  10.13  A.  M.,  his  second  attempt  to  walk  112  miles  in  24 
consecutive  hours.  At  6.51  p.m.  he  became  very  dizzy.  This  increased 
so  that  he  staggered  and  could  hardly  see  the  track.  After  6  rests  and  6 
attempts  to  continue  his  walk,  he  was  forced  to  abandon  the  attempt  at 
10.30  P.  M.  He  was  excessively  depressed  at  his  failure,  as  it  was  then 
impossible  for  him  to  accomplish  the  four  hundred  miles  in  five  days.     He 


4  12 

to 

9  59     " 

9  59 

to 

2  58  P.  M, 

258 

to 

3    3     " 

3    3 

to 

6  10     " 

6  10 

to 

613     " 

613 

to 

6  29     " 

6  29 

to 

639     " 

639 

to 

651     " 

651 

to 

703     " 

703 

to 

7  10     " 

7  10 

to 

806     " 

806 

to 

8  16     " 

8  16 

to 

821     " 

821 

to 

854     " 

854 

to 

9    2     " 

9    2 

to 

921 

9  21 

to 

931     " 

931 

to 

948     " 

948 

to 

10  21 

10  21 

to 

10  30     " 

10  30 

to 

12  00    M. 

404  EXCRETION    OF    NITROGEN 

took  a  little  food,  lay  down  and  went  to  sleep  about  midnight.  He  slept 
during  this  twenty-four  hours,  i  hour  ;  but  his  sleep  was  continued  into 
the  next  day. 

Walking  57  miles 12  h.     39  m.     34  sec. 

Defecation 3  " 

Urination 5  "       26   " 

Rest  on  the  track ...  41   " 

Rest  off  the  track 10"     31   " 

22  h.  119  m.     60  sec.  =  24  hours. 

Weights  and  Analyses  of  Food  and  Drink  for  the  Twenty- 
four  Hours 

Oz.  Av.  Nitrogen,  in  grains. 

Roast  beef 1.62  24,81 

Beef-essence 10.33  39-32 

Milk 8,75  25.27 

Bread 6.62  31.28 

Oatmeal-gruel 7-92  2 .  92 

Sugar 3.62  00.00 

Coffee 38.38  18.47 

Tea 30.06  2.63 

Lemonade 41.60  00.00 

§alt 0.08  00.00 

Pepper 0.05  00 .  00 

Bicarbonate  of  potash.  0.04  00.00 

149.07  144-70 

(4,225.61  grammes.)     (9.376  grammes.) 

Total  ingesta (9  lbs.,  $^1-^  oz.) 

Liquids (8  lbs.,  g^^-^  oz.) 

Analyses  of  Excretions  of  Twenty-four  Hours 

URINE 

Quantity 32.52  f^|   (965.0  cc.) 

Specific  gravity 1029. 6. 

Urea 688.98  grains,  44.641  grammes. 

Nitrogen  in  urea 321.52      "        20.832 

Uric  acid 9.21       "          0.597 

Phosphoric  acid 66.30      "          4.296 

Sulphuric  acid 32.66      "          2. 116 

Chloride  of  sodium 28.78      "          1.865 

This  urine  presented  a  faint  deposit  like  mucus  which  contained  a 
moderate  number  of  octahedra  of  the  o.xalate  of  lime  with  a  few  granules 
of  amorphous  urates. 

FECES 

Quantity 5.030Z.  av.     142.5      grammes. 

Nitrogen 21.01  grains,         1.750 

Nitrogen  in  urea  and  feces  combined.    348.53      "            22.582 
Nitrogen  of  urea  and  feces  per  100  parts  of  nitrogen  of  food.  240. 86   parts. 
Uric  acid  per  100  parts  of  urea i  •  33^ 


EXCRETION   OF   NITROGEN  405 

f  Weight  (naked) 114  lbs.  (51  k.  704  grammes.) 

I  Temperature  under  the  tongue 96-6"  (35.9'  C.) 

10.40  P.M.       \  p^j^^i^ 68 

Respirations 18. 


NOVEMBER    2=,,    FIFTH    DAY 

The  following  is  a  summary  of  the  twenty-four  hours 
of  November  25: 

12  00   to     9  56  A.  M.     9  h.  and  56  m.  rest  before  starting,  with  i  h.  30  m. 
of  November  24,  make  1 1  h.  26  m.  rest  for  the 
night  of  November  24  and  25. 
9  56   to    10  1 1      "         15  m.  walking  i  mile. 

10  II    to    10  16     "         5  minutes'  rest  in  room. 

10  16   to    10  58     "         42  m.  walking  3  miles,  with  i  m.  for  urination, 

10  58   to    II  21      "         23  minutes'  rest,  sitting  on  the  track. 

11  21    to    II  52     "         31  m.  walking  2I  miles. 

11  52   to   12  42  P.  M.      50  minutes'  rest  in  room. 

12  42   to      II      "         19  m.  walking   if  mile,  with  30  sec.  for  urina- 

tion. 

1  I    to      2  39     "         I  hour  38  minutes'  rest  in  room. 

2  39   to     419     "         I  h.  40  m.  walking  7  miles,  with  25  sec.  for  urina- 

tion. 
4  19   to     4  34     "         15  minutes'  rest  in  room. 
4  34   to     619     "         I  h.  and  45  m.  walking  8  miles,  with  2  stops  for 

urination,  averaging  29^^  sec.  each. 

6  19   to     7  43     "         I  hour  and  24  minutes'  rest  in  room. 

7  43   to     9  32     "         I  h.  and  49  m.  walking  9  miles,  with  40  sec.  for 

urination. 
9  32   to     9  50     "         18  minutes'  rest,  sitting  on  the  track. 
9  50  to    II  31      "         I  h.  and  41   m.  walking  7  miles,  with  2  stops  for 

urination,  averaging  25  sec.  each. 
II  31    to    II  41      "         10  minutes'  rest,  sitting  on  the  track. 

11  41    to    12  00  M.         19  m.  walking  1^  miles. 

During  the  twenty-four  hours  of  November  25,  Weston  walked  40^ 
miles  in  9  h.  and  i  m.,  including  4  m.  and  24  sec.  for  urination.  His 
walking-time  was  8  h.  56  m.  and  36  sec,  averaging  a  fraction  more  than 
4j  miles  per  hour.  He  had  51  minutes'  rest  sitting  on  the  track,  and  14 
h.  and  8  m.  rest  in  his  room.     He  urinated  on  the  track  7  times.     After 

12  M.,  he  was  in  remarkably  fine  condition.  He  made  several  rounds  in 
less  than  i  minute,  one  round  in  54  sec,  on  his  thirtieth  mile,  which  was 
done  in  8  m.  32  sec.  He  walked  about  i  mile  from  12  to  12.15  A.M., 
November  26.  At  the  conclusion  of  his  walk  he  was  in  the  best  of 
health  and  spirits.  He  slept,  during  the  twenty-four  hours,  9  hours 
and  26  minutes. 

Walking  4o|  miles  ...  8  h.       56  m.     36  sec. 

Urination 4  "       24   " 

Rest  on  the  track 51   " 

Rest  in  his  room 14  "         8  " 


22  h.     119  m.     60  sec.  =  24  hours. 


4o6 


EXCRETION    OF   NITROGEN 


TOTAL    MILES    WALKED 

Nov.  21 80  miles. 

"        22 48 

"        23 92        " 

"     24 57      " 

"     25 40J    " 

317^  miles. 

In  going  thirty-two  times  to  his  room,  Weston  walked,  in  addition  to 
the  above,  0.883  of  a  mile.  From  midnight,  November  25,  to  12.15  A.  M., 
November  26,  he  walked  i|  miles,  to  complete  his  five  days.  This,  with 
the  few  feet  to  the  urinal,  makes  about  320  miles  in  five  consecutive  days. 

Weights  and  Analyses  of  Food  and  Drink  for  the  Twenty- 
four  Hours 


Oz.  Av. 

Roast  beef 3 .  00 

Chicken n  .00 

Beef-essence 9  54 

Eggs 4-14 

Milk 9.78 

Bread 9.00 

Potatoes 4.00 

Oatmeal-gruel 3  •  39 

Butter 1 .25 

Sugar 2.37 

Tomatoes 3.12 

Coffee 27.27 

Tea 40. 08 

Lemonade 52.00 

Water 5.00 

Salt 0.08 

Pepper 0.05 


Nitrogen,  in  grains. 

45-94 
168.44 

36.31 
34.41 
28.24 
42.52 

5-77 
1.28 

3-50 

00.  GO 
00.00 
13.12 

3.51 
00.00 
00.00 
00.00 
00.00 


185.07  383.04 

(5,246.09  grammes.)    (24.818  grammes.) 

Total  ingesta di  lbs.,  9y^  oz.) 

Liquids (9  lbs.,  7y|o  oz.) 


Analyses  of  Excretions  of  Twenty-four  Hours 

URINE 

Quantity 43.60  fl§   (1,290.0  cc.) 

Specific  gravity 1022.6. 

Urea   657 .02  grains,  42 .  570  grammes. 

Nitrogen  in  urea 306.61       "        19.866 

Uric  acid o.  57      "  0.037 

Phosphoric  acid 57-49      "  3-725 

Sulphuric  acid 40 .  84      "  2 .  646 

Chloride  of  sodium 64.50      "  4.179 

This  urine  presented  a  whitish  grumous  sediment,  rather  copious, 
which  contained  a  few  octahedra  of  the  oxalate  of  lime  with  a  few  gran- 
ules of  amorphous  phosphates. 


EXCRETION   OF   NITROGEN  407 

FECES 

Quantity 4.87  oz.  av.     138.0     grammes. 

Nitrogen 26. 16  grains,         i  .695 

Nitrogen  in  urea  and  feces  combined .    332.77      "            21.561 
Nitrogen  of  urea  and  feces  per  100  parts  of  nitrogen  of  food.   84. 27    parts. 
Uric  acid  per  100  parts  of  urea 0.087     " 

1  Weight  (naked) 1 15-75  lbs.  (52  k.  497  grammes.) 

1.30  A.  M.         I  Temperature  under  the  tongue 97.9°  (36.6°  C.) 

Nov.  26.         "'  Pulse 80. 

[  Respirations 20 . 

THIRD  PERIOD,  FIVE  DAYS  AFTER  THE  WALK 

Notwithstanding  the  muscular  and  nervous  strain  to 
which  Weston  had  subjected  himself  for  the  past  five  days, 
culminating  on  the  fourth  day  in  complete  prostration  of 
the  nervous  system,  he  sat  up,  talked  and  joked  with  his 
friends  until  1.40  a.m.,  November  26,  then  went  to  bed 
and  slept  well  until  10  a.  m.  He  then  got  up,  "  feeling 
splendid,"  wakening  his  attendants,  who  were  almost  ex- 
hausted by  the  five  days'  labor  and  watching,  and  called 
for  his  breakfast,  which  he  ate  at  11.45,  ■^'^ith  excellent 
appetite.  For  the  succeeding  five  days  he  felt  as  well  as 
ever.  During  these  five  days  he  did  absolutely  nothing 
but  eat,  sleep  and  amuse  himself,  attending  to  no  business. 
He  took  no  exercise,  walking  only  about  two  miles  a  day, 
though  he  said  he  felt  as  if  he  could  walk  one  hundred  miles 
any  day  without  dif^culty.  The  history  of  this  period 
closed  our  investigations. 

NOVEMBER    26.    FIRST    DAY 

Weston  slept  well.  He  took  breakfast  at  11.45  a.m. 
and  dinner  at  6.45  p.  m.  He  smoked  six  cigars  during  the 
day.  He  walked  two  miles.  He  slept,  during  the  twenty- 
four  hours,  eight  hours  and  twenty  minutes. 

Weights  and  Analyses  of  Food  and  Drink  for  the  Twenty- 
four  Hours 

Oz.  Av.  Nitrogen,  in  grains. 

Turkey 7  50  114.84 

Chicken 5.12  78.40 

Fish 3.50  53.59 

Eggs 4.14  3441 

Milk 2.06  5.95 

Custard 3.25  18.20 

Ice-cream 3 -5°  19.60 

Bread 7.75  36.62 


4oS 


EXCRETION    OF    NITROGEN 


Oz.  Av. 

Potatoes 5 .  oo 

Butter 1 .88 

Sugar 0.88 

Cauliflower 3.00 

Cranberries 5 .00 

Celery i.oo 

Lettuce 1.25 

Grapes i .  00 

Apples 5.00 

Coffee 24.24 

Lemonade 14.68 

Water 30.00 

Salt 0.15 

Pepper 0.05 

129.95 


Nitrogen,  in  grains. 
7.22 
5.26 
00.00 
00.00 
00.00 
00.00 
00.00 
00.00 
00.00 
I  I  .56 
00.00 
00.00 
00.00 
00.00 


385.65 


(3,683.63  grammes.)    (24.987  grammes.) 

Total  ingesta (8  lbs.,     lyV^  oz.) 

Liquids (2  lbs.,  I4tV%  oz-) 

Analyses  of  Excretions  of  Twenty-four  Hours 

URINE 

Quantity 31  •  59  A  3  (937-5  cc) 

Specific  gravity 1025.8. 

Urea 593—3  grains,  38 . 437  grammes. 

Nitrogen  in  urea 276.84      "        17-937 

Uric  acid 0.48      "  0.031 

Phosphoric  acid 29.06      "  1.883 

Sulphuric  acid 49-53      "  3-209 

Chloride  of  sodium 66.41       "  4 -303 

This  urine  presented  a  rather  heavy,  whitish  sediment  in  considerable 
quantity  which  contained  granules  of  the  amorphous  urates  with  a  very 
few  octahedra  of  the  oxalate  of  lime. 


Quantity 3 .  5 1  oz.  av.     99.  5      grammes. 

Nitrogen 18.86  grains,      1.222 

Nitrogen  in  urea  and  feces  combined.  .    295.70      "          19. 159         " 
Nitrogen  of  urea  and  feces  per  100  parts  of  nitrogen  of  food.    76.68    parts. 
Uric  acid  per  100  parts  of  urea 0.081      " 

r  Weight  (naked) 118  lbs.  (53  k.  518  grammes.) 

12.10  A.  M.       )  Temperature  under  the  tongue 98.6°  (37°  C.) 

Nov.  27.  j  Pulse 76 . 

[  Respirations 22 . 

NOVEMBER    2J,     SECOND     DAY 

Weston  slept  well.  He  took  breakfast  at  10  a.  m.;  din- 
ner at  2  p.  M.;  and  supper  at  6.45  p.  m.  He  smoked  seven 
cigars  during  the  day.  He  walked  about  two  miles.  He 
slept,  during  the  twenty-four  hours,  eight  hours  and  fifteen 
minutes. 


EXCRETION    OF    NITROGEN  409 

Weights  and  Analyses  of  Food  and  Drink  for  the  Twenty- 
four  Hours 

Oz.  Av.  Nitrogen,  in  grains. 

Beefsteak 5.00  76.56 

Roast  beef 2.50  38.28 

Turkey 9.00  137.81 

Head-cheese 1.50  14.70 

Eggs 4.14  34.41 

Milk 5.14  14.87 

Bread 16.15  76. 31 

Cheese 1.13  20.28 

Potatoes 10.25  14.82 

Oysters 3-90  36.34 

Ice-cream 2.88  16.13 

Butter 2.75  7.70 

Sugar 1.56  00.00 

Tomatoes 5.25  00.00 

Cranberries 4.50  00.00 

Preserves 4-75  00.00 

Catsup 0.42  00.00 

Coffee ^9.19  9.23 

Tea 19.04  1.66 

Molasses-and-water. . .  21.45  00.00 

Water 40 .  00  00 .  00 

Salt 0.05  00,00 

Pepper 0.06  00.00 

180.61  499.10 

(5,119.66  grammes.)    (32.338  grammes.) 

Total  ingesta (11  lbs.,  4yVo  o^.) 

Liquids (6  lbs.,  S-^^   oz.) 

Analyses  of  Excretions  of  Twenty-four  Hours 

URINE 

Quantity 46.i4fl3   (1,365.0  cc.) 

Specific  gravity 1024.4. 

Urea 716.29  grains,  46.410  grammes. 


Nitrogen  in  urea 334 .  27 

Uric  acid 0.52 

Phosphoric  acid 46 .  93 

Sulphuric  acid 46.07 

Chloride  of  sodium 1 70 .  64 


21.658 
0.034 
3.041 
2.985 

II .056 


This  urine  presented  a  slight  sediment  of  a  whitish  appearance  which 
contained  a  few  octahedra  of  the  oxalate  of  lime  and  a  few  groups  of  small 
crystals  of  uric  acid. 

FECES 

Quantity 4.570Z.  av.     129.5      grammes. 

Nitrogen 24. 54  grains,         i .  590 

Nitrogen  in  urea  and  feces  combined.    358.81       "           23.248         " 
Nitrogen  of  urea  and  feces  per  100  parts  of  nitrogen  of  food.    71.81    parts. 
Uric  acid  per  100  parts  of  urea 0.072 

27 


4IO  EXCRETION    OF    NITROGEN 


II    p.  M. 


Weight  (naked) 120.25  lbs.  (54  k.  539  grammes.) 

Temperature  under  the  tongue 98.4°  (36.9°  C.) 

Pulse 73- 

Respirations 22. 


NOVEMBER    28,    THIRD    DAY 

Weston  slept  well.  He  took  breakfast  at  8.50  a.m.; 
dinner  at  4.15  r.  m.;  and  supper  at  7.45  p.  m.  He  smoked 
five  cigars  during  the  day.  He  walked  about  two  miles. 
He  slei^t,  during  the  twenty-four  hours,  eight  hours  and 
fifty  minutes. 
Weights  and  Analyses  of  Food  and  Drink  for  the  24  Hours 

Oz.  Av.  Nitrogen,  in  grains. 

Beefsteak 9.37  143-48 

Oysters 5.62  53.37 

Eggs 4-14  34-4I 

Milk 9.27  26.76 

Cream-cakes 3.37  18.97 

Bread 11.62  54.8o 

Cheese 1.25  22.53 

Potatoes 11.00  15.88 

Butter 2.75  7.70 

Sugar 2.78  00.00 

Tomatoes 3.75  00.00 

Sweet  pickles 2.18  00.00 

Apples 3.12  00.00 

Grapes 2.75  00.00 

Coffee 32.32  15.53 

Tea 16.03  1.40 

Salt 0.06  00.00 

Pepper 0.06  00.00 

Vinegar 0.25  00.00 

121.69  394-83 

(3,449.49  grammes.)    (25 .  582  grammes.) 

Total  ingesta (7  lbs.,  gf-^  oz.) 

Liquids (3  lbs.,  g^y^  oz.) 

Analyses  of  Excretions  of  Twenty-four  Hours 

URINE 

Quantity 84.18  fl|  (2,490.0  cc.) 

Specific  gravity 1019.7. 

Urea 768.61  grains,  49.800  grammes. 

Nitrogen  in  urea 358 .  68      "        23 .  240         " 

Uric  acid 0.31       "  0.020         " 

Phosphoric  acid 105.68      "  6.847 

Sulphuric  acid 53-57      "  3-471 

Chloride  of  sodium 622.58      "        40.338 

This  urine  presented  a  slight  sediment  of  a  whitish  appearance  which 
contained  a  few  octahedra  of  the  oxalate  of  lime  and  a  few  groups  of 
small  crystals  of  uric  acid. 


EXCRETION    OF    NITROGEN  411 

FECES 

Quantity 9. 53  oz.  av.     270.0     grammes. 

Nitrogen 51. 19  grains,        3.316 

Nitrogen  in  urea  and  feces  combined.   409.87      "  26.556         " 

Nitrogen  in  urea  and  feces  per  100  parts  of  nitrogen  of  food.  103.81    parts. 
Uric  acid  per  100  parts  of  urea 0.040     " 

I  Weight  (naked) 120.25  lbs.  (54  k.  539  grammes.) 

I  Temperature  under  tlie  tongue.. .....   99.3°  (37.4°  C.) 

■  -5      ■     ■       I  Pulse 70 . 

l^  Respirations 22 . 

NOVEMBER    2g,    FOURTH    DAY 

Weston  slept  well.  He  took  breakfast  at  9.35  a.m.; 
dinner  at  2  p.  m.;  supper  at  6.30  p.  m.;  and  a  second  supper 
(which  weighed  3  lbs.,  6.75  oz.  av.)  at  11. 15  p.m.  He 
smoked  five  cigars  during  the  day.  He  walked  about  two 
miles.  He  slept,  during  the  twenty-four  hours,  seven 
hours  and  thirty-five  minutes. 

Weights  and  Analyses  of  Food  and  Drink  for  the  Twenty- 
four  Hours 

Oz.  Av.  Nitrogen,  in  grains. 

Beefsteak 4.25  65.08 

Roast  beef ,.  2.75  42.11 

Chicken 15.00  229.69 

Eggs 4.14  34.41 

Milk   6.25  18.05 

Bread 18.63  88.03 

Potatoes 13-50  20.59 

Cheese i  .00  18.03 

Rice-pudding 14.75  77-15 

Butter 5.12  14-33 

Sugar 2.12  00 .  00 

Tomatoes 7.38  00.00 

Tomato-soup 8.00  00.00 

Celery i.oo  00.00 

Figs 2.37  9.54 

Apples 7.00  00.00 

Coffee 48 .  48  23 .  30 

Tea ^6.03  1.40 

Water 10.00  00.00 

Salt 0.16  00.00 

Pepper 0.08  00.00 

188.01  641.71 

(5,329.43  grammes.)    (41 .  578  grammes.) 

Total  ingesta (11  lbs.,  12-^^-0  oz.) 

Liquids (  5  lbs.,    8^^^  oz.) 


412  EXCRETION   OF    NITROGEN 

Analyses  of  Excretions  of  Twenty-four  Hours 

URINE 

Quantity 60.38  fl§  (1,786.000.) 

Specific  gravity 1022 .  5. 

Urea 744-3-  grains,  48.226  grammes. 

Nitrogen  in  urea 347-35      "        22 .  505 

Uric  acid 2.51       "  0.163 

Phosphoric  acid 50  -  76      "  3  -  289 

Sulphuric  acid 48-73      "  3-157 

Chloride  of  sodium 297.70      "        19.288 

This  urine  presented  hardly  any  sediment.  The  microscopical  exami- 
nation was  entirely  negative. 

FECES 

Quantity 6.61  oz.  av.     187.5      grammes. 

Nitrogen 35.54  grains,        2.303 

Nitrogen  in  urea  and  feces  combined.   382.89      "            24.808         " 
Nitrogen  of  urea  and  feces  per  100  parts  of  nitrogen  of  food.    59.67    parts. 
Uric  acid  per  100  parts  of  urea 0-337     " 

I  Weight*  (naked) 123.5  lbs.  (56  k.  13  grammes.) 

12.20  A.M.       I  Temperature  under  the  tongue 98.8°  (37. 1°  C.) 

Nov.  30.         I  Pulse 78 . 

1^  Respirations 24. 

NOVEMBER    3O,    FIFTH    DAY 

Weston  slept  well.  He  took  breakfast  at  9.15  a.  m.; 
dinner  at  1.45  p.  m.;  and  supper  at  6.15  p.  m.  He  smoked 
during  the  day,  six  cigars.  He  walked  about  three  miles. 
He  had  a  headache  all  the  evening.  He  slept,  during  the 
twenty-foiu"  hours,  seven  hours  and  forty-five  minutes. 
The  records  were  closed  at  midnight. 

Weights  and  Analyses  of  Food  and  Drink  for  the  Twenty- 
four  Hours 

Oz.  Av.  Nitrogen,  in  grains. 

Beefsteak 1.88  28.79 

Roast  beef 3.37  51.60 

Fish 3.00  45-94 

Milk 5.66  16.34 

Bread 21.00  99.22 

Potatoes 5.94  8.58 

Butter 4.12  11-54 

Sugar 1.88  00.00 

Tomatoes 3- 12  00.00 

Tomato-soup 8.00  00.00 

Figs 2.06  8.29 

Preserved  citron 2.25  00.00 

Coffee 24.24  11.65 

*  This  great  increase  in  weight  is  accounted  for  by  3  lbs.  6.75  oz.  of  food 
taken  at  11. 15  P.  M. 


EXCRETION    OF    NITROGEN  413 

Oz.  Av.  Nitrogen,  in  grains. 

Tea 16.03  1.40 

Salt 0.06  00.00 

Pepper 0.06  00.00 

102.67  283.35 

(2,910.34  grammes.)    (18.359  grammes.) 

Total  ingesta (6  lbs.,    6^^  oz.) 

Liquids (2  lbs.,  1 5^^^  oz.) 

Analyses  of  Excretions  of  Twenty-four  Hours 

URINE 

Quantity 68.39  fl  3   (2,023.0  cc.) 

Specific  gravity 1022.6. 

Urea ....  81 1 .48  grains,  52 .  598  grammes. 

Nitrogen  in  urea 378.69      "        24.546 

Uric  acid 3- 3°      "          0.214         " 

Phosphoric  acid 52.00      "          3.364         " 

Sulphuric  acid 47-20      "          3.058         *' 

Chloride  of  sodium 404.65      "        26.218 

This  urine  presented  a  cloudy  sediment  in  moderate  quantity  which 
contained  a  moderate  number  of  octahedra  of  the  oxalate  of  lime. 

FECES 

Quantity 7.41  oz.  av.     210.0     grammes. 

Nitrogen 39 .  80  grains,        2 .  579 

Nitrogen  in  urea  and  feces  combined.   418.49      "  27.125 

Nitrogen  of  urea  and  feces  per  100  parts  of  nitrogen  of  food.    147.69   parts. 

Uric  acid  per  100  parts  of  urea 0.406     " 

I  Weight  (naked) 120.75  lbs.  (54  k.  765  grammes.) 

J  Temperature  under  the  tongue 97.5°  (36.4°  C.) 

^^^-  I  Pulse 76. 

[  Respirations 24. 

CONSOLIDATED    TABLES 

I  propose  to  present,  in  a  series  of  consolidated  tables, 
the  complete  history  of  the  fifteen  days,  divided  as  before 
into  three  periods  of  five  days  each,  in  the  form  in  which 
they  will  be  made  use  of  in  Part  II.  in  making  the  final 
deductions.  I  present  them  in  this  form  complete,  so  that 
all  or  any  part  of  them  may  serve  as  material  for  the  use 
of  others.  The  cutaneous  and  pulmonary  exhalations  were 
estimated  by  subtracting  the  weight  of  urine  and  feces  from 
the  weight  of  ingesta;  and  to  this  result  adding  any  loss 
of  weight,  or  subtracting  from  it  any  gain  in  the  weight 
of  the  body  during  the  twenty-four  hours. 

The  weights  are  given  in  pounds  and  ounces  avoirdu- 
pois and  in  grains  troy.  The  equivalents  in  French  weights 
are  given  in  parentheses: 


414 


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EXCRETION    OF    NITROGEN 


423 


Table  D. — Daily  Averages  for  the  Three  Periods 
(French  weights  and  measures  in  parentheses) 


First  period — five  days 
before  the  walk. 


Second  period — five 
days  of  the  walk. 


Third  period — five 
days  after  the  walk. 


Weight 

Temperature 

Pulse 

Respiration 

Sleep 

Miles  walked. .  .  . 
Ingesta 

Nitrogen  of  food. 


Cutaneous  and  pul- 
monary exhalation 

Urine. 
Quantity , 

Specific  gravity. . . . 
Urea 

Nitrogen  in  urea. . . 

Uric  acid 

Phosphoric  acid . . . 

Sulphuric  acid.  .  .  . 

Chloride  of  sodium 


Loss  in  5  days — 
21.8  oz.  (593  gr.) 


Average  of  5  days- 
gg"  Fahr. 
(37-2'  C.) 
78 
22 

8  h.  5  m. 
8.2  miles 
100.50  oz. 
(2,848.82  gr.) 
33946  grains 
(21.994J 

61.63  oz. 
(1,690.91  gr.) 


37.84  fl.  oz. 

(1,134.0  cc.) 

1024.9 

628.24  grains 

(40.705) 

293.18 

(1S.729) 

2.26 

(0.127) 

50.14 
(3.262) 

41-57 
(2.693) 

159-45 
(10.331) 


Loss  in  5  days — 

52.2  oz.  (1,565  gr.) 
Loss  in  4  days — 

83.2  oz.  (2,358  gr.) 
Average  of  5  days — 

96.3  Fahr, 

(35.7°  C.) 

90 
21 

3  h.  17  m. 
63.5  miles 
171.47  oz. 
(4,860.57  gr.) 
234.76  grains 
(13. 211) 

138.41  oz. 

(3,875.18  gr.) 


Gain  in  5  days — 
80  oz.  (2,268  gr. 


Average  of  5  days- 
98.6    Fahr. 
(37°  C.) 
74 
23 

8  h.  29  m. 
2.2  miles 
144.59  oz. 
(4,098.62  gr.) 
440.93  grains 
(28.569) 

62.82  oz. 
(1,706.78  gr.) 


38.46  fl.  oz. 

(1,138.0  cc.) 

102S.7 

722.16  grains 

(46.S03) 

337-OI 

(21.841) 

3.00 

(0.194) 

76.63 

(4-965) 

53.50 

(3.666) 

65.08 

(4.217) 


58.14  fl.  oz. 
(1,720.3  cc.) 

1023.0 

726.79  grains 

(47.094) 

339.17 

(21.977) 

1.42 

(0.082) 

56.89 

(3-674) 
49.02 

(3.176) 
312.40 
(20.241) 


Feces. 
Quantity .... 


Nitrogen . 


4.08  oz. 
(115-6) 
21.91  grains 
(1.421) 


4.53  oz. 
(128.3) 
24.32  grains. 
(1.576) 


6.33  oz. 

(179.3) 
33.99  grains 
(2.202) 


Nitrogen  in  urea  and 
feces  combined. . . 


315.09  grains 
(20.149) 


361.52  grains 
(23.217) 


Nitrogen  of  ureaand 
feces  per  100  pts. 
of  nitrogen  of  food 


92.82  parts. 


153.99  parts 


Uric  acid  per   100 
pts.  of  urea 


0.360  parts 


0.415  parts 


373.15  grains 
(24.179) 


84.63  parts 


0.195  parts 


424 


EXCRETION   OF    NITROGEN 


Table  E. — Meteorological  Ohservations,  taken  at  the  Cooper  Union, 
New  York  City,  by  Prof.  Oran  W.  Morris 


1870. 

BAROMETER. 

THERMOMETER 

(Fahrenheit). 

Degree  of  humidity. 
Saturation  repre- 
sented by  100. 

WIND. 

MONTH 

AND 

Daily  readings  corrected 
and  reduced  to  32°  Fahr. 

Self-registering. 

'Z  c 

82.0 
78.0 
42.5 

42.0 

74-0 

60.0 

48.5 

72.0 

77.0 

79-3 

82.0 
89.0 

90  0 

88.5 

80.0 

General 
direction. 

SKY   AND 

ATMOS- 
PHERE. 

DAY. 

High- 
est. 

Lowest. 

Mean. 

46.0 
47.0 
42.0 

36.0 
43-0 

50.0 

48.0 

50.0 
44.0 

49.0 

50.0 
58.0 

58.0 
62.0 

46.0 

Low- 
est. 

35-0 
37-0 
29.0 

27.0 

33-0 

38.0 
39-8 

36.0 
33-0 

39-0 

40.0 
42.0 

44.0 
38.0 

34-0 

V 

tn 

c 
a 

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9.0 

10. 0 

12.0 
9.0 

14.0 
II. 0 

10. 0 

10. 0 
16.0 

14.0 
24.0 

12.0 

A.  M. 

NW 

W 

S  w 

w 

w 

S  w 

NE 

s  w 
w 

w 

NW 

w 

NW 

s  w 

NW 

p.  M. 

s  w 
w 
w 

w 

s  w 

w 

N  E 

w 
w 

s  w 

NW 
NW 

s  w 

NW 
S  E 

Nov. 

Q 

in. 

in. 

in. 

° 

Wed'day 

16 

30 . 065 

29.817 

29.911 

40.60 

Clear. 

Thursday 

17 

30.146 

30.059 

30.099 

43-16 

Lightcl'ds 

Friday 

18 

29.931 

29.857 

29.895 

61.36 

Slight  rain 
and  slight 
snow  6. 1 5 

P.   M. 

Saturday 

19 

29.907 

29-735 

29.827 

56.66 

Snow 
squalls. 
Clear  eve. 

Sunday 

20 

29.950 

29.932 

29.942 

43.20 

Clear  A.M. 

Cloudy 

eve. 

Monday 

21 
22 

30.167 

29-954 

30.029 

44.70 

Cloudy. 

Tuesday 

30.174 

29.623 

29.913 

73-70 

Rain  all 
day.   Gale 
eve. 

Wed'day 

23 
24 

29.763 

29-547 

29.624 

51-30 

Lightcl'ds 

Thursday 

29.892 

29.832 

29.861 

43-46 

Flying 
clouds. 

Friday 

25 

30.044 

29.745 

29.879 

48.83 

Clear  A.M. 
Cl'dy  and 
rain  10.15 

P.  M. 

Saturday 

26 
27 

28 

29-715 

29-477 

29.569 

63.13 

Rain  A.M. 
Lightcl'ds 

Sunday 

29.914 

29 . 803 

29.846 

46.40 

Clear.    2 

meteors 

eve. 

Monday 

30.067 

30.054 

30 . 060 

48.90 

Lightcl'ds 

Tuesday 

29 
30 

30.033 

29.811 

29-949 

60.76 

Lightcl'ds 
Slight  rain 
evening. 

Wed'day 

30.277 

30.181 

30.221 

46.43 

Lightcl'ds 
Clear  eve. 

The  height  of  the  cistern  of  the 
tide  water.     A  severe  gale 


barometer  is  considered  to  be  46  feet  above 
N.  E.,  and  very  high  tide,  on  the  22d. 


EXCRETION   OF    NITROGEN  425 


PART    II 

PHYSIOLOGICAL  DEDUCTIONS  FROM  THE  OBSERVATIONS 
TAKEN  BEFORE,  DURING,  AND  AFTER  THE  WALK  OF 
317^    MILES    IN    FIVE    CONSECUTIVE    DAYS 

The  data  obtained  during  the  three  periods,  five  days 
before,  five  days  during  and  five  days  after  this  walk,  en- 
able me  to  come  to  certain  conclusions  in  regard  to  physi- 
ological questions  of  interest,  particularly  the  influence  of 
muscular  exercise  upon  the  elimination  of  nitrogen.  In 
regard  to  the  influence  of  this  excessive  and  prolonged 
exertion  upon  the  weight  of  the  body,  the  temperature, 
circulation,  respiration,  nervous  system,  etc.,  the  informa- 
tion is  necessarily  more  incomplete  and  indefinite.  I  shall, 
however,  endeavor  to  make  use  of  the  facts  that  were  noted; 
although  the  main  object  was  to  study  the  relations  of  the 
nitrogen. 

The  phenomena  observed  relate  to  the  weight  of  the 
body,  temperature,  pulse  and  respirations,  in  so  far  as 
these  conditions  were  modified  by  exercise  and  sleep. 
Having  taken  daily  the  weights  of  the  ingesta,  the  excre- 
tions by  the  kidneys  and  intestines  and  the  weight  of  the 
body,  it  was  possible  to  calculate  the  amount  of  exhalation 
from  the  lungs  and  skin. 

WEIGHT    OF    THE    BODY 

It  is  well  known  that  by  regulating  the  diet  and  exer- 
cise, the  weight  may  be  modified  within  certain  limits;  and 
the  system  of  training  employed  by  athletes  is  supposed 
to  develop  to  the  highest  degree  the  muscular  power  and 
endurance.  The  principle  in  training  is  in  brief  to  regulate 
the  exercise  so  that  gradually  the  system  is  worked  daily 
as  much  as  can  be  endured  without  exhaustion;  and  to 
restrict  the  diet  to  rare,  lean  meats,  stale  bread  and  nitrog- 
enous articles,  eliminating  fatty  matters  and  reducing  the 
starchy  matters  to  a  minimum.  By  this  process  the  weight 
is  reduced — for  professional  athletes  out  of  training  are  gen- 
erally over-weight — the  muscles  are  hardened,  nearly  all 
the  fat  disappears,  and  the  power,  and  within  limits  the 
endurance,  are  developed  to  a  maximum.  In  the  case  of 
AVeston  no  rigid  system  of  training  was  adopted;  but  the 

23 


426  EXCRETION    OF   NITROGEN 

changes  in  weight  are  interesting  in  view  of  the  great 
variations  in  his  diet  during  the  three  periods  and  the  dif- 
ferences in  the  amount  of  exercise  taken. 

When  the  investigations  were  begun,  at  midnight,  No- 
vember 15,  the  weight  was  120.5  l^s.  (54  k.  655  grammes). 
At  the  end  of  the  five  days  it  had  been  reduced  to  119.:^ 
lbs.  (54  k.  62  grammes).  The  hghtest  weight  during  this 
period  was  on  the  fourth  day,  when  it  was  118.5  lbs.  (53. 
k.  745  grammes).  On  the  second  day  the  weight  increased 
to  121.25  l^s.  (55  kilos.). 

First  Period,  Five  Days  before  the  Walk. — On 
the  first  day,  the  weight  being  unchanged,  Weston  walked 
fifteen  miles;  he  took  122.99  oz.  (3,492.17  grammes)  of 
food  and  drink,  containing  361.22  grains  (23.404  grammes) 
of  nitrogen.  He  discharged  44.20  oz.  (1,303.08  grammes) 
in  the  urine  and  feces,  and  78.79  oz.  (2,189.09  grammes) 
by  the  lungs  and  skin.  The  weather  was  clear  and  dry, 
the  temperature  ranging  between  35°  and  46°  Fahr.  As- 
suming the  usual  quantity  of  food  and  drink  for  an  ordi- 
nary man  to  be  about  90  oz.  (2,542  grammes),  containing 
about  310  grains  (20  grammes)  of  nitrogen,*  rather  an 
excess  was  taken  on  this  day.  The  cutaneous  exhalation 
was  excessive.  Allowing  20  oz.  (567  grammes)  for  pul- 
monary exhalation,  which  is  fairly  constant,  the  cutaneous 
exhalation  amounted  to  58.70  oz.  (1,658.27  grammes),  the 
normal  amount  being  about  30  oz.  (850  grammes). f 

On  the  second  day  there  was  a  diminution  in  the  total 
quantity  of  food  and  drink  and  in  the  quantity  of  nitrogen 
(total  food  and  drink,  105.43  oz.  [2,987.92  grammes]* 
nitrogen,  288.35  grains  [18.682  grammes]),  with  an  in- 
crease in  weight  of  12  oz.  (345  grammes),  the  urine  and 
feces  being  diminished  about  0.5  oz.  (15.13  grammes),  and 
the  cutaneous  exhalation  about  29  oz.  (834.12  grammes). 
The  weather  was  a  little  warmer,  but  cloudy  and  damp. 
The  only  explanation  I  can  offer  for  this  increase  in  weight 
is  in  the  exercise,  which  was  only  five  miles. 

On  the  third  day  there  was  a  loss  in  weight  of  20  oz. 
(567  grammes).     On  this  day  there  was  a  further  diminu- 

*  Flint,  "Physiology  of  Man,"  New  York,  1867,  vol.  ii.,  Alimentation,, 
p.  124. 

f  /(/.,  1866,  vol.  1.,  Respiration,  p.  447  ;  and,  Id.,  1870,  vol.  iii..  Secretion, 
p.  139- 


EXCRETION    OF    NITROGEN  427 

tion  in  the  quantity  of  food  and  drink  and  in  the  nitrogen 
(total  food  and  drink,  86.56  oz.  [2,453.67  grammes] ;  nitro- 
gen 272.27  grains  [17.641  grammes]).  The  urine  and 
feces  were  increased  by  about  8.25  oz.  (243.58  grammes), 
and  the  cutaneous  exhalation,  4.88  oz.  (142.17  grammes). 
The  exercise  was  five  miles,  the  same  as  on  the  second 
day. 

On  the  fourth  day  the  weight  was  diminished  24  oz. 
(687  grammes).  The  total  quantity  of  food  was  about  the 
same  as  on  the  third  day  (86.19  oz. — 2,443.19  grammes). 
The  nitrogen  was  increased  by  about  63  grains  (4.065 
grammes).  The  urine  and  feces  were  diminished  by  about 
15.5  oz.  (455.03  grammes),  and  the  cutaneous  exhalation 
was  increased  by  about  19  oz.  (549.55  grammes).  The 
exercise  on  this  day  was  fifteen  miles,  wdiich,  with  the 
diminished  ingesta,  will  account  for  the  loss  in  weight. 

On  the  fifth  day  there  was  a  gain  in  weight  of  about 
II  oz.  (317  grammes).  The  total  quantity  of  food  and 
drink  w'as  increased  over  the  quantity  on  the  fourth  day 
by  about  15  oz.  (429.44  grammes).  The  nitrogen  was 
increased  by  more  than  105  grains  (6.830  grammes).  The 
urine  and  feces  were  about  the  same  as  on  the  fourth  day. 
The  cutaneous  exhalation  was  diminished  by  22.27  o^- 
(680.02  grammes).  The  exercise  on  this  day  was  only  one 
mile.  The  increase  in  w'eight  is  to  be  explained  only  by 
the  want  of  exercise  and  the  large  quantity  of  solid  food 
taken. 

Second  Period,  Five  Days  of  the  Walk. — This 
period  presents  the  greatest  interest  as  regards  the  influ- 
ence of  the  diet  and  exercise  upon  the  weight  of  the 
body. 

On  the  first  day,  walking  eighty  miles  and  sleeping  but 
one  hour,  the  loss  of  weight  was  about  45  oz.  (1,224.00 
grammes).  The  quantity  of  food  and  drink  was  increased 
over  the  quantity  on  the  day  before  by  about  85  oz.  (2,409.- 
75  grammes),  the  increase  being  chiefly  in  liquids.  The 
nitrogen  was  diminished  by  289  grains  (18,716  grammes). 
The  feces  were  but  slightly  increased.  The  urine  was  in- 
creased by  about  8  oz.  (195  cc).  The  estimated  cutaneous 
exhalation  was  increased  by  130  oz.  (3,723.11  grammes), 
a  little  more  than  two  and  a  half  times.  The  loss  in  weight 
was  undoubtedlv  due  in  a  ereat  measure  to  the  extraordi- 


428  EXCRETION    OF   NITROGEN 

nary  amount  of  exercise.  I  shall  endeavor  to  explain  this 
more  fully  when  I  compare  the  weights  for  the  three 
periods. 

On  the  second  day,  walking  forty-eight  miles  and 
sleeping  4  hours  and  28  minutes,  there  was  a  further  loss 
of  4  oz.  (114  grammes).  The  quantity  of  food  and  drink 
was  diminished  by  about  21  oz.  (582.25  grammes),  but  the 
nitrogen  was  increased  by  about  114  grains  (7.409 
grammes).  The  feces  were  increased  by  a  little  more  than 
3  oz.  (89  grammes).  The  urine  was  diminished  by  about 
8.5  oz.  (254  cc).  The  cutaneous  exhalation  was  dimin- 
ished by  54  oz.  (1,521.38  grammes).  The  loss  of  weight 
I  shall  endeavor  to  explain  farther  on. 

On  the  third  day,  walking  ninety-two  miles  and  sleep- 
ing but  thirty  minutes,  the  loss  of  weight  was  estimated 
at  20  oz.  (567  grammes).  The  weight  was  not  accurately 
taken  on  this  day  and  was  averaged. 

On  the  fourth  day,  walking  fifty-seven  miles  and  sleep- 
ing one  hour,  the  weight  was  36  oz.  (1,020.00  grammes) 
less  than  on  the  second  day.  (This  represents  the  loss  for 
two  days.)  The  food  and  drink  were,  for  the  third  day, 
about  5  oz.  (151.09  grammes)  more  than  for  the  second 
day,  and  for  the  fourth  day,  about  22  oz.  (625.61  grammes) 
less  than  for  the  third  day.  On  the  third  day  the  nitrogen 
was  diminished  by  about  37  grains  (2.417  grammes).  On 
the  fourth  day  the  nitrogen  was  further  diminished  by  84 
grains  (5.436  grammes).  There  were  no  feces  on  the  third 
day,  and  the  urine  was  increased  by  about  7  oz.  (209  cc). 
On  the  fourth  day  the  feces  were  in  about  average  quan- 
tity. The  urine  was  diminished  about  8  oz.  (235  cc).  On 
the  third  day  the  cutaneous  exhalation  w-as  increased  by 
about  22  oz.  (610.82  grammes).  On  the  fourth  day  the 
cutaneous  exhalation  was  diminished  by  about  23  oz. 
(636.67  grammes).  I  shall  discuss  the  loss  of  weight  in 
connection  with  a  comparison  of  the  three  periods. 

On  the  fifth  day,  walking  forty  and  a  half  miles  and 
sleeping  9  hours  and  26  minutes,  there  was  an  increase  in 
weight  of  28  oz.  (793.00  grammes).  The  food  and  drink 
were  increased  by  36  oz.  (1,020.48  grammes).  The  nitro- 
gen was  increased  by  239  grains  (15.442  grammes),  about 
two  and  two-thirds  times.  The  feces  were  diminished  by 
0.16  oz.  (4.50  grammes),  and  the  urine  was  increased  by 


EXCRETION    OF    NITROGEN  429 

about  1 1  oz.  (325  cc).  The  cutaneous  exhalation  was 
diminished  by  about  19  oz.  (546.61  grammes). 

The  loss  of  weight  during  this  period  of  extraordinary 
muscular  exertion  is  an  interesting  question;  and  it  will 
be  considered  in  connection  with,  not  only  the  quantities 
of  food,  drink,  excretions  and  exhalations,  but  the  quan- 
tities of  nitrogen  introduced  and  discharged. 

Third  Period,  Five  Days  after  the  Walk. — It  is 
to  be  remembered  that  this  period  was  one  of  nearly  abso- 
lute repose  after  the  exertion  of  the  preceding  five  days, 
with  a  daily  average  of  eight  and  a  half  hours  of  sleep. 

On  the  first  day  the  w'eight  increased  by  36  oz.  (1,021.00 
grammes).  The  weight  of  food  and  drink  was  dinjinished 
by  about  55  oz.  (1,662.46  grammes),  but  the  quantity  of 
nitrogen  was  about  the  same  as  on  the  fifth  day  of  the 
second  period.  The  feces  w^ere  diminished  by  1.36  oz. 
(38.50  grammes),  and  the  urine,  by  about  12  oz.  (352.50 
cc).  The  cutaneous  exhalation  was  diminished  by  nearly 
50  oz.  (1,394.50  grammes).  The  increase  in  weight  was 
probably  due  in  greatest  part  to  retention  of  liquids  and 
appropriation  of  nitrogenous  matters  to  supply  the  mus- 
cular waste  that  had  been  going  on  for  the  previous  five 
days.  For  the  five  days  of  the  walk,  for  every  100  parts  of 
nitrogen  of  food  there  was  a  discharge  of  174.81  parts  in 
the  urine  and  feces.  On  this,  the  first  day,  the  discharge 
of  nitrogen  was  in  the  proportion  of  76.68  parts  per  100 
parts  in  the  food. 

On  the  second  day  there  was  a  further  gain  in  weight  of 
36  oz.  (1,021.00  grammes),  which  brought  the  weight  to 
120.25  lbs.  (54  k.  539  grammes),  about  the  weight  at  the 
beginning  of  the  observations,  which  was  120.5  l^^s.  (54  k. 
655  grammes).  The  w-eight  of  food  and  drink  was  in- 
creased by  50.66  oz.  (1,436.03  grammes),  and  the  nitrogen 
was  increased  by  about  113  grains  (7.351  grammes).  The 
feces  w-ere  increased  by  about  i  oz.  (28.35  grammes),  and 
the  urine,  by  about  14.5  oz.  (427.15  cc).  The  cutaneous 
exhalation  was  increased  by  about  34  oz.  (969.41  grammes). 
This  day  was  warm,  clear  and  dry,  the  first  day  being  rainy 
and  5°'^to  8°  Fahr.  colder. 

On  the  third  day  the  weight  was  unchanged.  The  food 
and  drink  were  diminished  by  59  oz.  (1,670.17  grammes), 
and  the  nitrogen,  by  about  104  grains  (6.756  grammes). 


430  EXCRETION   OF   NITROGEN 

The  feces  were  increased  by  5  oz.  (140.5  grammes),  a  little 
more  than  doubled.  The  urine  was  increased  by  38  oz. 
(1,125  cc-)'  nearly  doubled.  The  cutaneous  exhalation 
was  diminished  by  about  66.5  oz.  (1,930.61  grammes), 
more  than  three  times.  This  day  shows  a  working  off 
by  the  urine  and  feces  of  the  unusual  amount  of  food, 
especially  nitrogenous  matter,  taken  on  the  previous  day, 
the  weight  remaining  stationary. 

On  the  fourth  day  the  weight  was  increased  by  52  oz. 
(1,474.00  grammes).  This  great  increase  is  explained  by 
the  following  circumstance:  At  11. 15  p.m.  Weston  took 
supper,  the  food  and  drink  weighing  54.75  oz.  (1,547.36 
grammes).  The  weight  of  the  body  was  taken  at  11.55 
p.  M.,  about  the  usual  hour.  This  was  the  only  time  when 
anything  was  eaten  after  7.45  p.  m.  This  accident  renders 
it  useless  to  discuss  the  question  of  weight  on  this  day. 
On  this  day  the  nitrogen  of  the  food  was  largely  increased, 
amounting  to  641.71  grains  (41,578  grammes),  the  average 
for  an  ordinary  man  being  about  310  grains  (20  grammes). 

On  the  fifth  day  the  weight  was  about  the  same  as  on 
the  third  day,  the  increase  being  only  0.5  lb.  (226 
grammes).  On  this,  the  final  day  of  the  observations,  the 
weight  was  about  the  same  as  on  the  first  day  of  the  first 
period,  being  increased  only  a  quarter  of  a  pound.  The 
food  and  drink  were  diminished  by  about  85  oz.  (2,419.09 
grammes),  and  the  nitrogen,  by  about  358.5  grains  (23,219 
grammes).  The  feces  were  increased  by  about  i  oz.  (22.5 
grammes),  and  the  urine,  by  8  oz.  (237  cc).  The  cuta- 
neous exhalation  was  increased  by  about  1.68  oz.  (37.87 
grammes). 

Causes  of  the  Variations  in  Weight.* — In  a  meas- 
ure, the  variations  in  weight  during  the  fifteen  days  may 
be  satisfactorily  explained;  but  there  are  certain  questions 
involved  that  are  as  yet  obscure.  The  explanation  of  the 
variations  during  the  walk  and  for  the  five  days  after  is 
much  facilitated  by  a  comparison  of  the  ingress  and  egress 
of  nitrogen. 

At  the  beginning  of  the  investigations  the  weight  was 
120.5  lbs.,  which  Weston  thought  was  about  normal.    Dur- 

*  To  avoid  complicating  the  discussion  of  the  causes  of  the  variations  in 
weight,  the  English  weights  only  will  be  used. 


EXCRETION    OF    NITROGEN  431 

ing  the  period  of  five  days  before  the  walk  the  variations 
were  not  very  great,  the  highest  being  12  oz.  above,  and 
the  lowest,  32  oz.  below.  At  the  end  of  the  fifth  day  the 
weight  was  reduced  by  about  21  oz.  On  the  first  day,  the 
weight  being  unchanged,  the  exercise  was  fifteen  miles. 
The  food  was  of  the  usual  variety,  but  its  quantity  and 
proportion  of  nitrogen  were  about  30  per  cent,  above  the 
average  for  an  ordinary  man.  On  the  second  day  the  di- 
minished exercise,  the  food  being  less  but  still  above  the 
normal  average,  will  account  for  the  increase  in  weight  of 
12  oz.  On  the  third  day  the  exercise  was  the  same  as  on 
the  second  day;  but  the  food  was  reduced  a  little  below 
the  normal  average,  which  will  account  for  20  oz.  loss  of 
weight.  On  the  fourth  day  the  food  was  still  below  the 
average,  being  about  the  same  as  on  the  previous  day;  but 
it  contained  a  large  proportion  of  nitrogenous  matter,  20 
per  cent,  more  than  on  the  third  day.  The  exercise  was 
fifteen  miles,  which,  with  the  diet,  will  account  for  24  oz. 
loss  of  weight.  On  the  fifth  day  the  food  was  increased 
to  a  little  above  the  average,  and  it  contained  a  large  quan- 
tity of  nitrogen,  about  35  per  cent,  above  the  average. 
This  fact,  with  the  absolute  muscular  repose  and  ten  hours' 
sleep  as  a  preparation  for  the  walk,  will  readily  account 
for  1 1  oz.  increase  in  weight.  During  this  period  of  five 
days  before  the  walk  the  average  quantity  of  food  and 
drink  was  100.5  oz.,  containing  339.46  grains  of  nitrogen, 
the  ordinary  average  being  90  oz.,  containing  310  grains 
of  nitrogen.  The  average  discharge  of  nitrogen  by  the 
urine  and  feces  was  95.53  parts  per  100  parts  of  the  nitro- 
gen of  food,  which  is  about  normal.  Thus  it  is  evident 
that  the  variations  in  weight  during  a  period  of  five  days 
of  ordinary  life  can  be  explained  in  accordance  with  gen- 
erally accepted  physiological  principles. 

In  endeavoring  to  explain  the  variations  in  weight  that 
occurred  during  the  walk,  and  for  the  succeeding  five  days, 
the  extraordinary  muscular  exertion  introduces  new  ele- 
ments to  be  considered.  These  have  an  important  bearing 
upon  the  subject  of  nutrition,  disassimilation  and  "  the 
source  of  muscular  power,"  about  which  so  much  has  been 
written  within  the  last  few  years. 

First:  What  tissue  was  consumed,  the  products  being 
thrown  of¥,  during  the  effort  of  walking  317?  miles  in  five 


432  EXCRETION    OF   NITROGEN 

consecutive  days?  Was  it  the  muscular  substance?  The 
importance,  as  regards  the  processes  of  nutrition,  of  a  defi- 
nite answer  to  this  question  can  hardly  be  overestimated. 

The  loss  of  weight  was  undoubtedly  due  in  great  meas- 
ure to  the  excessive  muscular  exertion,  but  in  part,  also, 
to  change  in  diet. 

The  loss  must  have  been  either  in  liquids,  fats  or  mus- 
cular substance. 

It  is  not  probable  that  the  loss  was  due  in  any  great 
degree  to  a  diminution  in  the  proportion  of  liquids,  for 
the  excessive  loss  from  the  skin  was  supplied  by  liquids 
taken  into  the  stomach.  It  is  not  necessary  to  cite  experi- 
ments which  show  that  loss  by  the  skin,  as  it  occurs  in 
hot-air  or  vapor-baths  or  in  working  for  an  hour  or  more 
at  a  high  temperature,  is  readily  compensated  by  liquid 
ingesta,  as  this  fact  is  well  settled  in  physiology.*  A  glance 
at  the  daily  tables  of  food  and  drink  will  show  that  during 
the  five  days  of  the  walk  Weston  took  8  lbs.  8  oz.  to  lo  lbs. 
II  oz.  of  liquids. 

If  the  loss  was  due  to  a  consumption  of  non-nitroge- 
nous matters,  it  would  be  chiefly  of  fat  and  would  be  rep- 
resented by  the  carbonic  acid  of  expiration.  It  is  certain 
that  the  non-nitrogenous  constitutents  of  the  body  do  not 
contribute  to  the  formation  of  the  nitrogenous  excremen- 
titious  matters. 

If  the  loss  was  due  to  a  consumption  of  the  nitrogenous 
constituents  of  the  body,  principally  of  the  muscular  tissue, 
this  loss,  under  the  extraordinary  muscular  effort,  would 
be  represented  by  the  nitrogen  of  the  excretions.  It  is 
not  probable  that  the  nitrogenous  constituents  of  the  body 
are  in  any  considerable  amount  changed  into  non-nitrog- 
enous matter  and  exhaled  in  the  form  of  carbonic  acid, 
though  this  probably  does  occur  to  some  extent. 

The  question  then  resolves  itself  to  one  of  the  relative 
consumption  and  elimination  of  nitrogenous  matters.  The 
following  are  the  facts  on  this  point,  obsen^ed  during  the 
five  days  of  the  walk: 

During  the  five  days  of  the  walk  f  Weston  consumed 
in  all,  1,173.80  grains  (76.055  grammes)  of  nitrogen  in  his 

*  See  my  work  on  Physiology,  New  York,  1870,  vol.  iii.,  p.  140  et  seq. 
f  I  have  reduced  these  calculations,  on  account  of  their  great  importance,  to 
grammes. 


EXCRETION   OF   NITROGEN  433 

food.  During  the  same  period  he  ehminated  1,807.60 
grains  (116.084  grammes)  of  nitrogen  in  the  urine  and 
feces.  This  leaves  633.80  grains  (40.030  grammes)  of  nitro- 
gen, over  and  above  the  nitrogen  of  the  food,  which  must 
be  attributed  to  the  waste  of  his  tissues,  and  probably  al- 
most exclusively  to  the  waste  of  his  muscular  tissue.  Ac- 
cording to  the  best  authorities,  lean  meat  uncooked,  or 
muscular  tissue,  contains  3  per  cent,  of  nitrogen.*  The 
loss  of  633.80  grains  (40.030  grammes)  of  nitrogen  would 
then  represent  a  loss  of  21,127.00  grains  (1.334.33 
grammes),  or  3.018  lbs.  of  muscular  tissue.  The  actual 
loss  of  weight  was  3.450  lbs.  (1,565.00  grammes).  This 
allows  about  0.43  lb.  (230.67  grammes)  loss  unaccounted 
for,  which  might  be  fat  or  water. 

The  correspondence  of  these  figures  of  loss  calculated 
from  the  quantity  of  nitrogen  eliminated  with  the  actual 
loss  in  weight  leaves  little  room  for  doubt  in  regard  to 
the  fact  that  the  immense  exertion  during  this  period  of 
five  days  was  attended  with  consumption  of  muscular  sub- 
stance. Those  who  have  adopted  the  view  that  the  mus- 
cular system  is  like  a  steam-engine,  consuming  in  its  work 
food  as  fuel  and  not  its  own  substance,  may  say  that  this 
is  an  extraordinary  case,  as  it  undoubtedly  is;  but  the  facts 
developed  by  the  foregoing  observations  prove,  none  the 
less  conclusively,  that  the  muscular  system  may  consume 
its  own  substance  by  exercise,  even  when  the  individual 
takes  all  the  food  required  by  his  appetite.  It  can  hardly 
be,  however,  that  the  foregoing  facts  are  not  in  accordance 
with  a  general  physiological  law. 

It  will  be  interesting,  now,  to  study  the  behavior  of  the 
system  after  the  walk,  when  there  was  almost  absolute  re- 
pose and  when  the  quantity  of  nitrogen  taken  with  the 
food  was  largely  increased.  The  important  question  here 
is  the  following: 

In  the  return  of  the  weight  to  the  normal  standard,  did 
the  muscular  tissue  take  up  nitrogen  to  repair  the  excessive 
waste  engendered  by  the  five  days  of  exertion? 

In  two  days  after  the  walk  the  weight  had  increased  to 
within  four  ounces  of  the  weight  at  the  beginning  of  the 
observ^ations,  five  days  before  the  walk.     It  is  not  to  be 

*  Payen,  "  Precis  theorique  et  pratique  des  substances  alimentaires,"  Paris, 
1865,  p.  48S. 


434  EXCRETION    OF   NITROGEN 

expected  that  this  increase  would  be  due  entirely  to  appro- 
priation of  nitrogenous  matter  by  the  muscular  system. 
Reference  to  the  tables  of  diet  for  these  two  days  shows 
that  the  food  taken  was  about  155  oz.  each  day,  the  normal 
average  being  assumed  at  90  oz.,  an  excess  of  a  little  more 
than  70  per  cent.  The  nitrogen  taken  was  about  50  per 
cent,  in  excess  of  the  normal  quantity.  The  tables  also 
show  a  large  proportion  of  non-nitrogenous  matter  in  the 
food  on  those  days.  The  exercise  was  only  two  miles  daily. 
Weston  gained  in  weight  4.5  lbs.  He  retained  in  his  sys- 
tem a  quantity  of  nitrogen  equivalent  to  i.i  lb.  In  view 
of  the  muscular  inactivity  and  the  large  proportion  of  Jion- 
nitrogenous  matter  in  the  food,  it  is  fair  to  assume  that  the 
remaining  3.4  lbs.  were  due  to  accumulation  of  fat.  This, 
however,  is  a  point  incapable  of  positive  demonstration. 
Taking  the  entire  period  of  five  days  after  the  walk,  the 
gain  in  weight  was  five  pounds,  which  brought  it  to  4  oz. 
above  the  weight  at  the  beginning  of  the  fifteen  days.  The 
excess  of  the  nitrogen  of  food  over  the  nitrogen  of  the 
urine  and  feces  represented,  for  these  five  days,  an  accu- 
mulation of  1.6  lb.  of  muscular  substance.  During  this 
time  there  was  almost  complete  repose  of  the  muscular 
system.  The  daily  quantity  of  food  was  about  61  per  cent, 
over  the  normal  average,  and  the  nitrogen,  about  42  per 
cent,  over  the  average.  The  food  contained,  also,  a  large 
proportion  of  non-nitrogenous  matter. 

These  facts  seem  to  indicate  that  after  the  effort  in 
walking  317I  miles  in  five  consecutive  days,  for  five  days 
of  muscular  inactivity,  the  quantity  of  food  being  large 
and  containing  a  greater  proportion  of  non-nitrogenous 
matter  than  the  food  taken  either  before  or  during  the 
walk,  the  muscular  system  appropriated  1.6  lb.  of  nitroge- 
nous matter,  and  the  entire  body  accumulated  about  3.4 
lbs.  of  fat.  It  is  well  known  that  athletes,  after  a  season 
of  severe  training  by  exercise  and  nitrogenous  diet,  accu- 
mulate fat  very  rapidly,  when  the  muscles  are  allowed 
repose  and  the  diet  is  unrestricted. 

TEMPERATURE,    PULSE    AND    RESPIRATIONS 

The  temperature  under  the  tongue  for  every  day  during 
the  three  periods  was  carefully  taken,  as  nearly  as  possible 
at  the  same  hour  and  under  the  same  conditions.     During 


EXCRETION   OF    NITROGEN  435 

the  five  days  of  the  walk  the  temperature  was  taken  after 
the  day's  walk  had  been  accomplished;  and  during  the  five 
days  before  and  the  five  days  after  the  walk  it  was  taken 
generally  between  10.45  ^-  ^^-  ^^*i  midnight. 

First  Period,  Five  Days  before  the  Walk. — The 
temperatures  for  each  day  do  not  present  any  great  range 
of  variation.  The  data  here  are  useful  chiefly  as  indicating 
the  normal  average  under  ordinary  conditions.  The  high- 
est temperature  was  at  the  end  of  the  first  day.  It  was 
then  99.7°  Fahr.  (37.6°  C).  The  lowest  temperature  was 
on  the  third  day,  when  it  was  98°  Fahr.  (36.7°  C).  On 
the  first  day  the  quantity  of  food  and  drink  and  the  pro- 
portion of  nitrogen  were  above  the  average  by  about  20 
per  cent.  The  exercise  was  fifteen  miles.  On  the  third 
day  the  quantity  of  food  and  drink  was  a  very  little  below 
the  average,  and  less  nitrogen  was  taken  than  on  any  of  the 
five  days.  The  exercise  was  five  miles.  On  the  fifth  day 
the  temperature  was  within  0.2°  Fahr.  of  the  temperature 
on  the  first  day.  On  this  day  the  quantity  of  food  and  drink 
was  slightly  above  the  average,  but  the  nitrogen  of  the 
food  was  increased  by  42  per  cent.  The  exercise  was  only 
one  mile.  On  the  first  day  the  weather  was  clear,  the  high- 
est temperature  in  the  shade  was  46°  and  the  lowest,  35° 
Fahr.  On  the  fifth  day  it  also  was  clear,  and  the  highest 
temperature  was  43°  and  the  lowest,  30°  Fahr.  On  the 
third  day  the  meteorological  record  was,  "  slight  rain  and 
slight  snow  6.15  p.  m.,"  highest  temperature  42°.  and  low- 
est 29°  Fahr.  On  the  fourth  day,  when  the  temperature 
under  the  tongue  was  99.1°  Fahr.  (37.3°  C),  the  external 
temperature  was  36°,  highest,  and  2y°,  lowest,  "snow- 
squalls,  clear  evening."  On  this  day  the  total  quantity  of 
food  and  drink  was  the  same  as  on  the  third  day,  but  the 
nitrogen  of  the  food  was  increased  by  about  23  per  cent. 
On  the  fourth  day  the  exercise  was  fifteen  miles.  On  the 
second  day,  when  the  temperature  under  the  tongue  was 
98.4°  Fahr.  (36.9°  C),  the  nitrogen  of  the  food  was  only 
16.08  grains  more  than  on  the  third  day.  The  weather 
was  cloudy,  the  highest  temperature,  47°  and  the  lowest, 
7^y°  Fahr. 

In  the  range  of  temperature  during  the  five  days  of  this 
period,  there  does  not  seem  to  be  any  marked  difference 
due  to  the  exercise.    The  variations  apparently  bear  some 


436  EXCRETION    OF    NITROGEN 

relation  to  the  quantity  of  nitrogenous  food,  the  tempera- 
ture being  high  when  the  nitrogen  of  the  food  is  abundant 
and  low  when  the  proportion  is  small.  The  temperature 
w^as  markedly  higher  on  the  clear  days,  without  any  defi- 
nite relation  to  the  external  temperature. 

The  range  of  temperature  for  these  five  days  was  about 
normal,  98°  to  99.7°  Fahr.  (36.7°  to  37.6°  C).  In  my 
work  on  physiology  I  have  taken,  as  the  standard  tem- 
perature under  the  tongue,  98°  Fahr.,  subject  to  varia- 
tions within  the  limits  of  health  of  about  0.5"  below  and 
1.5°  above.* 

The  average  temperature  for  the  first  period  of  five 
days  before  the  walk,  which  I  shall  take  as  the  standard 
for  comparison  with  the  temperatures  at  the  other  periods, 
is  99°  Fahr.  (37.2°  C). 

Second  Period,  Five  Days  of  the  Walk. — The 
variations  in  temperature  during  this  period  are  remark- 
able, and  are  highly  interesting  from  their  possible  physi- 
ological relations.  By  reference  to  the  meteorological 
table  (E.),  it  will  be  seen  that  the  weather  during  this 
period  was  generally  cloudy,  without  much  variation  from 
day  to  day  in  the  thermometer.  There  does  not  appear  to 
be  any  constant  relation,  during  this  period,  between  the 
temperature  and  the  daily  consumption  of  nitrogen. 

On  the  first  day,  between  12.15  ^-  M-  ^^^  ^^-S-i  P-  M- 
Weston  walked  eighty  miles.  His  temperature  was  taken 
eight  minutes  after  he  had  completed  the  walk,  and  was 
95.3°  Fahr.  (35.3°  C),  4.3°  less  than  the  last  temperature 
taken  before  the  walk  was  begun.  This  is  a  large  reduc- 
tion, greater  than  ever  occurs  under  the  ordinarv  condi- 
tions of  health;  and  it  can  be  attributed  only  to  the  ex- 
traordinary muscular  exertion  during  the  day. 

On  the  second  day,  between  4.58  a.  m.  and  4.5  p.  m., 
Weston  walked  forty  miles,  when  he  stopped  for  6  hours 
and  19  minutes.  At  10  p.  m.,  about  six  hours  after  the 
stop,  the  temperature  was  94.8°  Fahr.  (34.9°  C),  a  reduc- 
tion from  the  temperature  of  the  first  day  of  0.5°.  Weston 
did  not  sleep  well,  as  he  had  hoped  to  do  during  the  six 
hours.  At  10.24  p.  M.  he  began  his  first  effort  to  walk  one 
hundred  and  twelve  miles  in  twenty-four  consecutive  hours. 

*  "  Physiology  of  Man,"  New  York,  1870,  vol.  iii.,  Nutrition,  p.  396. 


EXCRETION   OF   NITROGEN  437 

I  now  think  the  further  lowering  in  the  temperature  was 
an  indication  of  want  of  proper  reaction  after  the  walks  he 
had  already  accomplished.  Had  I  appreciated  the  facts  at 
that  time,  I  should  have  advised  him  to  defer  his  attempt 
to  accomplish  the  hundred  and  twelve  miles  until  a  later 
period.     As  it  was,  the  attempt  was  a  failure. 

As  on  the  first  day  the  lowering  in  temperature  is  to 
be  attributed  only  to  the  excessive  and  prolonged  muscu- 
lar exertion. 

On  the  third  day,  between  midnight  of  the  second  day 
and  10.52  p.  M.,  Weston  walked  ninety-two  miles.  At  11. 15 
p.  M.  the  temperature  was  96.6°  Fahr.  (35.9°  C),  1.8° 
higher  than  on  the  second  day. 

On  the  fourth  day  Weston  walked  fifty-seven  miles  be- 
tween 1.33  A.  M.  and  10.30  P.  M.  The  temperature,  taken 
at  10.40  P.  M.,  was  96.6°  Fahr.  (35.9°  C),  the  same  as  on 
the  third  day.  This  was  the  day  on  which  the  walk  was 
interrupted  by  breaking  down. 

On  the  fifth  day  Weston  walked  forty  and  a  half  miles 
between  9.56  a.  m.  and  midnight.  He  continued  walking 
for  fifteen  minutes  after  midnight.  He  was  in  fine  spirits 
all  day.  During  this  twenty-four  hours,  for  the  first  time, 
he  got  sufficient  refreshing  sleep.  He  slept  nine  hours  and 
twenty-six  minutes.  The  temperature,  taken  at  1.30  a.  m. 
of  the  next  day,  was  97.9°  Fahr.  (36.6°  C);  an  increase 
of  1.3°  over  the  temperature  of  the  day  before. 

It  is  difiicult  to  explain  satisfactorily  the  elevation  of 
temperature  by  1.8°  on  the  third  day,  the  day  of  the  longest 
walk,  and  the  same  temperature  on  the  fourth  day,  when 
Weston  broke  down  completely.  The  temperature,  how- 
ever, on  these  days  was  still  2.4°  below  the  average  of  the 
five  days  before  the  walk,  and  2°  below  the  average  of  the 
five  days  after  the  walk.  The  elevation  in  temperature 
on  the  fifth  day,  by  1.3°,  was  probably  on  account  of  the 
sleep  of  nine  hours  and  twenty-six  minutes. 

The  average  temperature  during  this  period  was  96.3° 
Fahr.  (35.7°  C);  2.7°  below  the  average  of  five  days  be- 
fore, and  2.3°  below  the  average  of  five  days  after  the 
walk.  The  nearly  uniform  depression  of  temperature  dur- 
ing this  period  of  excessive  exertion  shows  pretty  con- 
clusively that  severe  and  prolonged  muscular  exercise  di- 
minishes the  heat  of  the  body.     It  has  been  observed  that 


438  EXCRETION    OF   NITROGEN 

during  or  immediately  after  moderate  exercise,  the  heat 
of  the  body  is  increased;  and  that  the  actual  temperature 
of  the  muscles  is  sensibly  elevated;*  but  this  is  quite  dif- 
ferent from  the  great  muscular  and  nervous  strain  to  which 
Weston  subjected  himself  for  five  days.  The  fact  of 
diminution  of  temperature  during  this  period  remains, 
therefore,  without  any  explanation,  except  that  it  was 
probably  due  to  some  unusual  condition  of  the  nervous 
system. 

Third  Period,  Five  Days  after  the  Walk. — Dur- 
ing this  period  there  was  but  little  variation  in  the  tem- 
perature from  day  to  day.  On  the  first  day  the  tempera- 
ture was  98.6°  Fahr.  (37°  C),  0.7°  higher  than  on  the 
last  day  of  the  walk.  This  temperature  was  about  normal. 
On  the  second  day  the  temperature  was  98.4°  Fahr.  (36.9^ 
C);  on  the  third  day,  99.3°  Fahr.  (37.4°  C);  on  the 
fourth  day,  98.8°  Fahr.  (37.1°  C);  and  on  the  fifth  day, 
97.5°  Fahr.  (36.4°  C).  This  range  of  temperature 
was  about  normal,  assuming,  as  I  have  done,  that  the 
average  is  98°  Fahr.,  with  a  range  of  0.5°  below  and  1.5° 
above.  The  average  temperature  for  the  five  days  was 
98.6°  Fahr.  (37°  C),  0.4°  less  than  "the  average  for  the 
five  days  before  the  walk  and  2.3°  more  than  the  average 
for  the  five  days  of  the  walk. 

In  studying  the  variations  in  temperature  from  day  to 
day  during  this  period,  I  have  not  been  able  to  find  any 
definite  relation  with  the  food  or  with  the  meteorological 
record.  The  difference  between  the  average  during  this 
period  and  the  average  for  the  five  days  before  the  walk 
is  insignificant.  It  is  interesting  to  note,  however,  that  so 
soon  as  the  extraordinary  muscular  effort  ceased,  the  tem- 
perature returned  to  about  the  normal  standard. 

Pulse  and  Respirations. — During  the  first  period 
there  was  very  little  variation  in  either  the  pulse  or  respi- 
rations. The  extremes  for  the  pulse  were  93  and  71.  The 
pulse  was  93  just  before  the  walk;  and  this  probably  was 
due  to  excitement  incident  to  the  occasion.  At  that  time, 
also,  the  respirations  were  25.  For  the  first  three  days 
the  respirations  were  20,  and  on  the  fourth  day,  23. 

*  For  an  account  of  different  observations  on  this  point,  see  my  work  on. 
Physiology,  New  York,  1870,  vol.  iii.,  Nutrition,  p.  413. 


EXCRETION   OF   NITROGEN  439 

During  the  five  days  of  the  walk  the  pulse  ranged  be- 
tween 68  and  109.  The  pulse  was  109  on  the  third  day, 
when  the  exercise  was  ninety-two  miles.  The  range  of 
the  respirations  was  between  18  and  23.  On  the  fourth 
day,  after  Weston  had  completely  broken  down  in  his  walk, 
the  pulse  was  68  and  the  respirations  18. 

For  the  five  after  the  walk  the  range  of  the  pulse  was 
between  70  and  78,  and  the  respirations  were  between 
22  and  24. 

The  averages  for  the  five  days  before  the  walk  were, 
for  the  pulse,  78,  respirations  22;  for  the  five  days  of  the 
walk,  pulse  90,  respirations  21;  and  for  the  five  days  after 
the  walk,  pulse  74,  respirations  23. 

In  the  absence  of  sphygmographic  records  of  the  pulse, 
there  could  be  little  learned  from  the  observations  on  the 
circulation.  The  variations  in  the  respirations,  also,  con- 
vey little  information.  It  was  impossible,  however,  to  make 
the  records  on  these  points  more  elaborate;  and  as  it  was 
necessary  to  make  all  of  the  observations  without  sub- 
jecting Weston  to  any  considerable  annoyance  or  loss  of 
time,  experiments  with  the  sphygmograph  would  have 
been  impracticable. 

The  records  in  regard  to  sleep,  exercise,  quantity  of 
food  and  drink  and  the  composition  of  the  food  were  made 
to  be  used  in  connection  with  the  question  of  the  elimina- 
tion of  nitrogen,  and  will  not,  therefore,  be  discussed  sepa- 
rately. The  cutaneous  and  pulmonary  exhalations  were 
calculated  from  the  weight  of  ingesta,  urine  and  feces  and 
the  variations  in  the  weight  of  the  body.  As  these  were 
not  directly  estimated  they  will  not  be  discussed  under 
distinct  heads. 

VARIATIONS  IN  THE  URINE  DUE  TO  EXERCISE,  STUDIED 
IN  CONNECTION  WITH  THE  PROPORTION  OF  NITROGEN 
IN  THE  FOOD 

In  discussing  the  variations  in  the  urine  during  the 
three  periods  into  which  the  investigations  were  divided.  I 
shall  take  up  first  the  quantity;  then  the  urea,  or  the  quan- 
tity of  nitrogen  eliminated  in  the  urea,  in  connection  with 
the  nitrogen  of  the  feces,  and  compare  the  total  elimination 
of  nitrogen  with  the  quantity  introduced  with  the  food; 


440  EXCRETION    OF    NITROGEN 

then  the  uric  acid  and  its  relations  to  the  urea;  and  finally, 
the  inorganic  salts  and  abnormal  matters. 

QUANTITY    OF    URINE 

The  most  important  point  to  determine  in  this  connec- 
tion is  whether  the  immense  amount  of  exercise  during  the 
five  days  of  the  walk  had  any  influence  on  the  elimination 
of  water  by  the  kidneys.  This  can  be  settled  with  tolerable 
accuracy,  inasmuch  as  the  liquids  taken  each  day  were  care- 
fully measured. 

First  Period,  Five  Days  before  the  Walk. — The 
range  of  variation  in  the  quantity  of  urine  during  this  period 
was  not  great,  the  extremes  being  32.45  fl  5  (960  cc.) 
and  46.15  flo  (1.365  cc).  The  variations  do  not  present 
any  definite  relation  to  the  quantity  of  liquids.  On  the 
fourth  day,  with  32.45  fl  3  of  urine,  the  liquids  taken 
amounted  to  68.73  ^  5-  On  the  third  day,  w4th  46.15  flo 
of  urine,  the  liquids  taken  amounted  to  55.56  fl  o-  On 
the  third  day,  when  the  quantity  of  urine  was  the  greatest, 
the  meteorological  record  is  the  following:  Thermometer, 
highest,  42°  Fahr.,  lowest,  29°  Fahr. ;  humidity  (saturation 
100)  61.36;  "slight  rain  and  slight  snow  at  6.15  p.m." 
The  humidity  on  that  day  was  the  greatest  of  the  five. 
On  the  fourth  day,  when  the  quantity  of  urine  was  the 
least,  the  record  was  as  follows:  Thermometer,  highest, 
36°  Fahr.,  lowest,  27°  Fahr.;  humidity  56.66;  "snow- 
squalls,  clear  evening."  During  this  period  the  excess 
of  liquids  taken  must  have  been  discharged  through  the 
skin. 

The  average  quantity  of  urine  during  these  five  days 
was  37.84  fl  o  (1,134  cc).  The  average  quantity  of  liquids 
taken  daily  was  65.56  fl  o  (1,966.8  cc). 

Second  Period,  Five  Days  of  the  Walk. — The 
range  of  variation  in  the  quantity  of  urine  during  this  pe- 
riod also  was  slight,  the  extremes  being  43.60  fl§  (1,290 
cc),  on  the  fifth  day,  and  32.52  fl  o  (965  cc),  on  the 
fourth  day.  The  variations  bore  no  definite  relation  to 
the  meteorological  record.  On  the  day  of  greatest  dis- 
charge of  urine,  the  liquids  taken  amounted  to  151.06  fl  o- 
On  the  day  of  the  least  urine,  the  liquids  taken  amounted 
to  137.04  flo-     During  this  period  the  relations  between 


EXCRETION    OF    NITROGEN  441 

the  quantity  of  urine  and  of  liquids  taken  were  pretty  con- 
stant: first  day,  urine,  42.09  flS;  liquids  taken,  171.67  flo; 
second  day,  urine,  33.50  115;  liquids  taken,  136.40  flo; 
third  day,  urine,  40.56  flo;  liquids  taken,  158.75  flo; 
fourth  day,  urine,  32.52  flS;  liquids  taken,  137.04  flo; 
fifth  day,  urine,  43.60  flo;  liquids  taken,  151.06  fl  5. 

The  average  quantity  of  urine  during  these  five  days 
was  38.46  flo  (1,138  cc).  The  average  quantity  of  liquids 
taken  was  150.40  flo  (4.512  cc). 

The  average  of  38.46  flo  (1,138  cc.)  for  the  five  days 
of  the  walk,  against  38.14  fl  o  (i,i34  cc),  for  the  five  days 
before  the  walk,  shows  that  the  walk  of  317^  miles  in  fiv.e 
days  did  not  affect  the  quantity  of  urine,  and  that  the 
large  quantities  of  liquids  taken  during  that  time  must  have 
been  discharged  by  the  skin. 

Third  Period,  Five  Days  after  the  Walk. — The 
variations  in  the  daily  discharge  of  urine  during  this  period 
were  very  considerable,  the  extremes  being  84.18  fl  o  (2,490 
cc),  on  the  third  day,  and  31.59  flo  (937.5  cc),  on  the 
iirst  day.  The  variations  bore  no  definite  relation  to  the 
meteorological  record.  There  was  no  definite  relation  be- 
tween the  quantity  of  urine  and  the  liquid  ingesta.  On  the 
third  day,  with  84.18  fl  ,3  of  urine,  the  liquids  taken 
amounted  to  57.87  fl  B;  and  on  the  first  day,  with  31.59  fl  o 
of  urine,  the  liquids  taken  amounted  to  46.74  fl  5.  On 
the  second  day  the  liquids  taken  amounted  to  104.82  flo, 
and  the  urine  discharged,  46.14  fl  o- 

The  average  quantity  of  urine  during  these  five  days 
was  58.14  fl  o  (1,720  cc).  The  average  quantity  of  liquids 
taken  was  69.22  fl  §  (2,076  cc). 

During  the  five  days  after  the  walk,  for  every  100  parts 
of  liquid  ingesta  the  kidneys  discharged  84  parts.  During 
the  five  days  before  the  walk,  for  every  100  parts  of  liquid 
ingesta  the  kidneys  discharged  58  parts.  This  is  probably 
to  be  explained  by  the  exercise  of  8.2  miles  daily  for  the 
five  days  before  the  walk,  which  would  increase  the  action 
of  the  skin,  while  after  the  walk  the  exercise  was  only  2.2 
miles  daily. 

It  will  not  be  necessar}^  to  consider  under  a  separate 
head  the  variations  in  the  specific  gravity  of  the  urine,  as 
this  simply  represents  the  solid  constituents,  which  will  be 
taken  up  separately. 
29 


442  EXCRETION   OF   NITROGEN 

INFLUENCE  OF  EXERCISE  UPON  THE  ELIMINATION  OF 
NITROGEN,  CHIEFLY  IN  THE  UREA,  AND  THE  RELATIONS 
BETWEEN  THE  NITROGEN  DISCHARGED  AND  THE  NITRO- 
GEN   INGESTED 

As  regards  the  elimination  of  nitrogen,  the  investiga- 
tions were  undertaken  chiefly  with  reference  to  the  influ- 
ence of  the  great  muscular  exertion  during  the  five  days 
of  the  walk.  In  order  to  ascertain  exactly  the  quantity 
of  nitrogen  excreted  at  this  time  as  compared  with  that 
discharged  under  ordinary  conditions,  the  nitrogen  of  both 
the  urea  and  feces  was  taken.  The  proportion  of  nitrogen 
in  the  uric  acid,  creatin  and  creatinin  of  the  urine  is  so 
insignificant,  as  compared  with  the  total  discharge,  that 
it  would  hardly  modify  the  results  of  the  calculations.  Dur- 
ing the  fifteen  days  Weston  took  food  according  to  his 
fancy.  At  certain  times  during  the  walk  he  took  large 
quantities  of  tea  and  coffee;  but  the  results  of  the  calcula- 
tions show  that  the  modifications,  if  any,  in  the  discharge 
of  urea  produced  by  these  articles  must  have  been  greatly 
overshadowed  by  those  due  to  the  muscular  exercise.  In 
the  discussion  of  this,  the  most  important  of  the  questions 
involved,  the  influence  of  food  will  be  treated  of  from  a 
secondary  point  of  view.  As  regards  this  point  there  is 
no  difference  of  opinion.  Nitrogenous  food  always  in- 
creases the  elimination  of  urea;  and  so  marked  is  this,  that 
many  physiologists  hold  the  view  that  urea  is  derived  al- 
most entirely  from  the  food.  This  is  one  of  the  physiolog- 
ical questions  settled  by  these  observations. 

From  the  foregoing  considerations  it  is  evident  that 
the  only  accurate  way  to  determine  the  modifications  in  the 
elimination  of  nitrogen  that  are  to  be  attributed  to  muscu- 
lar exercise,  is  to  calculate  for  each  period,  and  for  every 
day  of  each  period,  the  proportion  borne  by  the  nitrogen 
in  the  urea  and  feces  to  the  nitrogen  of  the  food.  It  is 
true  that  the  influence  of  the  food  of  one  day  may  be  pro- 
longed for  one  or  more  days,  and  the  same  remark  may 
possibly  apply  to  the  exercise;  but  the  periods  of  five  days 
each  are  sufficiently  long  to  obviate  any  serious  error  from 
this  cause.  I  have  learned,  however,  from  these  calcula- 
tions, that  a  period  much  shorter  would  not  be  entirely 
satisfactorv. 


EXCRETION    OF    NITROGEN  443 

The  conclusions  that  I  shall  arrive  at  will  all  be  drawn 
from  Tables  A.^  B.^  C.^  for  the  first  period;  Tables  A.^ 
B.-  C.^  for  the  second  period;  and  Tables  A.^  B.^  C.^  for 
the  third  period.  Table  D.  gives  the  daily  averages  for 
the  three  periods. 

First  Period,  Five  Days  before  the  Walk. — For 
the  first  day  of  this  period  the  total  nitrogen  of  the  urea 
and  feces  was  323.26  grains  (20.945  grammes).  The  nitro- 
gen of  the  food  was  361.22  grains  (23.404  grammes).  For 
every  100  parts  of  nitrogen  of  food,  there  were  discharged 
in  the  urea  and  feces, -89.49  parts.  The  exercise  was  fifteen 
miles.  The  nitrogen  of  the  food  was  about  30  per  cent, 
above  the  average  for  an  ordinary  man.  The  elimination 
of  nitrogen  per  100  parts  of  the  nitrogen  of  food  was  con- 
siderably below  the  average. 

On  the  second  day  the  total  nitrogen  of  the  urea  and 
feces  was  301.18  grains  (18. 181  grammes).  The  nitrogen 
of  the  food  was  288.35  grains  (18.682-  grammes).  For 
every  100  parts  of  nitrogen  of  food,  there  were  discharged 
in  the  urea  and  feces,  104.45  parts.  The  exercise  was  five 
miles.  The  nitrogen  of  the  food  of  this  day  was  a  little 
below  the  average. 

On  the  third  day  the  total  nitrogen  of  the  urea  and 
feces  was  330.36  grains  (21.405  grammes).  The  nitrogen 
of  the  food  was  272.27  grains  (17.641  grammes),  much  be- 
low the  average  for  an  ordinary  man,  which  I  put  at  310 
grains.  For  every  100  parts  of  nitrogen  of  food,  there 
W'Cre  discharged  in  the  urea  and  feces.  12 1.3  parts.  The 
exercise  was  five  miles. 

On  the  fourth  day  the  total  nitrogen  of  the  urea  and 
feces  was  300.57  grains  (19.475  grammes).  The  nitrogen 
in  the  food  was  335.01  grains  (21.706  grammes),  a  little 
above  the  average  for  an  ordinary  man.  For  every  100 
parts  of  nitrogen  of  food,  there  were  discharged  in  the 
urea  and  feces,  89.75  parts.  The  exercise  was  fifteen 
miles. 

On  the  fifth  day  the  total  nitrogen  of  the  urea  and 
feces  was  320.06  grains  {20.'j}^y  grammes).  The  nitrogen 
of  the  food  was  440.43  grains  (28.536  grammes),  much 
above  the  average.  For  every  100  parts  of  nitrogen  of 
food,  there  were  excreted  in  the  urea  and  feces,  72.67  parts. 
The  exercise  was  one  mile,  with  ten  hours'  sleep. 


444  EXCRETION    OF    NITROGEN 

Taking  the  averages  for  the  five  days,  the  nitrogen  of 
the  urea  and  feces  daily  was  315.09  grains  (20. 149  grammes). 
The  daily  nitrogen  of  the  food  was  339.46  grains  (21.994 
grammes).  For  every  100  parts  of  nitrogen  of  food,  there 
were  excreted  in  the  urea  and  feces,  92.82  parts,  which  may 
be  taken  as  about  the  normal  average  under  ordinary  con- 
ditions. 

From  these  figures,  the  following  conclusions  may  be 
drawn : 

I.  Under  ordinary  conditions  about  93  per  cent  of  the 
nitrogen  of  food  is  represented  in  the  urea  and  feces;  and 
the  remaining  7  per  cent,  may  be  put  down  to  nitrogen 
discharged  in  other  ways  and  to  an  allow^ance  for  error  in 
the  estimates,  particularly  in  the  food. 

II.  In  view^  of  the  unusual  power  of  endurance  of  Wes- 
ton and  his  habit  of  walking  long  distances,  I  do  not  think 
that  the  variations  in  the  exercise  during  the  five  days  are 
to  be  regarded  as  sufficient  to  influence,  to  any  great  ex- 
tent, the  elimination  of  nitrogen;  and  I  consider  that  these 
variations  are  due  chiefly  to  the  nitrogen  of  the  ingesta. 
The  influence  of  the  food  probably  is  manifested  in  a  more 
marked  manner  one  or  two  days  after  than  on  the  day  on 
which  the  excess  of  nitrogen  is  taken.  This  fact  has  been 
recognized  by  physiologists,  especially  since  the  researches 
of  Lehmann,  to  which  reference  has  already  been  made.* 
On  the  first  day  there  was  about  30  per  cent,  of  excess 
of  nitrogen  of  the  food,  and  89.49  parts  of  nitrogen  dis- 
charged per  100  parts  of  nitrogen  taken  in.  On  the  sec- 
ond and  third  days  the  nitrogen  of  the  food  was  a  little 
below  the  average.  On  these  days  there  was  an  average 
of  1 1 1.65  parts  of  nitrogen  discharged  per  100  parts  of 
nitrogen  taken  in.  On  the  fourth  day  the  nitrogen  of  the 
food  was  slightly  in  excess,  with  89.75  parts  'per  100  dis- 
charged. On  the  fifth  day  the  nitrogen  in  the  food  was 
very  largely  in  excess  (42  per  cent.),  with  72.67  parts  per 
100  discharged.  The  absolute  quantity  of  nitrogen  dis- 
charged on  the  fifth  day  was  large,  but  the  proportion  per 
100  of  the  nitrogen  of  food  was  overbalanced  by  the  large 
quantity  introduced. 

What  is  the  mechanism  of  the  influence  of  nitrogenous 

*  Lehmann,  "  Physiological  Chemistry,"  Philadelphia,  1855,  vol.  i.,  p.  150. 


EXCRETION    OF    NITROGEN  445 

food  upon  the  discharge  of  nitrogen  by  the  excretions? 
Does  the  excremental  nitrogen  come  from  a  direct  change 
of  the  nitrogenous  constituents  of  the  blood  into  urea  in 
the  blood  itself,  or  is  it  derived  from  the  nitrogenous  food 
used,  through  the  blood,  in  building  up  the  nitrogenous 
semisolids  of  the  body,  passing  into  the  excretions  through 
the  processes  of  nutrition  and  disassimilation? 

Although  the  answers  to  these  questions  are  perhaps 
beyond  the  limits  of  actual  demonstration,  the  attainable 
facts  point  very  strongly  to  the  following: 

The  nitrogenous  food  occupies  several  hours  in  its  di- 
gestion and  its  appropriation  by  the  blood,  where  it  is 
changed  into  the  nitrogenous  nutritive  constituents  of  the 
circulating  fluid.  The  process  of  its  appropriation  by  the 
nitrogenous  constituents  of  the  tissues,  particularly  in  the 
muscular  system,  is  probably  slower  still.  The  chief  prod- 
uct of  disassimilation  of  the  nitrogenous  constituents  of 
the  tissues  is  urea;  and  its  separation  is  very  slow  and  grad- 
ual. This  fact  is  illustrated  by  the  slow  accumulation  of 
urea  in  the  blood  after  extirpation  of  the  kidneys.  If  this 
is  the  mechanism  of  the  production  of  urea,  the  increase  in 
its  quantity  would  be  marked  for  a  day  or  two  after  the  in- 
troduction of  an  excess  of  nitrogenous  food;  and  this  is  a 
fact  demonstrated  by  actual  observation.  If  the  excess  of 
urea  were  directly  formed  in  the  blood  from  an  excess  of 
nitrogenous  food,  being  discharged  by  the  urine  and  leav- 
ing a  stated  and  but  slightly  variable  quantity  resulting 
from  the  actual  disassimilation  of  the  tissues,  its  increased 
discharge  from  an  excess  of  nitrogenous  food  would  be 
more  rapidly  developed. 

Second  Period,  Five  Days  of  the  Walk. — On  the 
first  day  of  this  period  Weston  walked  eighty  miles,  with 
one  hour  of  sleep.  The  total  nitrogen  of  the  urea  and  feces 
was  357.10  grains  (22.167  grammes).  The  nitrogen  of  the 
food  was  reduced  more  than  50  per  cent,  below  the  average, 
being  only  151.55  grains  (9.820  grammes).  For  every  100 
parts  of  nitrogen  introduced  there  were  235.63  parts  of 
nitrogen  discharged. 

This  very  great  discharge  of  nitrogen  in  proportion  to 
the  nitrogen  of  the  food  may  be  in  part  explained  by  the 
large  excess  of  nitrogen  taken  the  day  before;  but  by  far 
the  greatest  part  can  be  attributed  only  to  the  extraordi- 


446  EXCRETION    OF    NITROGEN 

nary  ninscnlar  exertion  and  the  consequent  waste  of  mus- 
cular tissue.  The  loss  of  weight  on  the  first  clay  was  43.2 
oz.  (1,224.00  grammes). 

On  the  second  day  Weston  walked  forty-eight  miles, 
with  4  hours  and  28  minutes  of  sleep.  The  total  nitrogen 
of  the  urea  and  feces  was  370.64  grains  (24.015  grammes). 
The  nitrogen  of  the  food  was  largely  increased,  being 
265.92  grains  (17.229  grammes).  For  every  100  parts  of 
nitrogen  introduced,  there  were  discharged,  139.39  parts. 
On  this  day  there  was  still  a  large  excess  of  nitrogen  dis- 
charged; but  the  proportion  per  100  parts  of  the  nitrogen 
introduced  was  reduced  by  the  increase  in  the  proportion 
in  the  food.  The  excessive  discharge  of  nitrogen  on  this 
day  is  to  be  attributed  almost  exclusively  to  the  muscular 
exertion  of  that,  and,  perhaps,  of  the  previous  day. 

On  the  third  day  Weston  walked  ninety-two  miles,  with 
30  minutes  of  sleep.  The  entire  quantity  of  nitrogen  of 
the  urea  (no  feces  were  passed)  was  very  large,  amounting 
to  397.58  grains  (25.760  grammes),  representing  851.95 
grains  (55.200  grammes)  of  urea,  by  far  the  largest  quantity 
discharged  in  any  one  of  the  five  days.  This  corresponded 
to  the  greatest  amount  of  muscular  exertion,  a  fact  which  is 
very  significant.  The  nitrogen  of  the  food  was  slightly 
diminished,  amounting  to  228.61  grains  (14.812  grammes). 
For  every  100  parts  of  nitrogen  introduced,  there  were  dis- 
charged, 173.91  parts.  This  excessive  discharge  of  nitro- 
gen can  be  attributed  only  to  the  muscular  exertion.  On 
that  day  Weston  took  six  pints  of  strong  coffee,  which, 
if  it  had  any  effect,  would  have  diminished  the  elimination 
of  urea. 

On  the  fourth  day  Weston  walked  fifty-seven  miles, 
with  one  hour  of  sleep.  The  nitrogen  of  the  urea  and  feces 
was  348.53  grains  (22.582  grammes).  The  nitrogen  of  the 
food  was  on  this  day  diminished  to  the  minimum,  being 
only  144.70  grains  (9.376  grammes).  For  every  100  parts 
of  nitrogen  introduced,  there  were  discharged,  240.86  parts, 
the  largest  excess  observed  during  the  five  days. 

At  10.30  p.  M.,  on  this  day,  Weston  broke  down  com- 
pletely. He  could  not  see  the  track  and  was  taken  stag- 
gering to  his  room,  having  reached  apparently  the  limit 
of  his  endurance.  His  condition  at  that  time,  as  shown  by 
the  records,  was  as  follows:  He  had  lost  in  weight  83.2 


EXCRETION   OF   NITROGEN  447 

oz.  (2.358.00  grammes),  being  reduced  from  119.2  lbs.  (54 
k.  62  grammes)  to  114  lbs.  (51  k.  704  grammes).  He  had 
taken  a  daily  average  of  197.70  grains  (12.809  grammes) 
of  nitrogen  in  his  food,  while  walking  an  average  of  sixty- 
nine  and  a  quarter  miles  per  day,  with  an  average  of  sleep 
in  each  twenty-four  hours  of  i  hour  and  44  minutes,  for 
four  days.  His  daily  average  of  nitrogen  should  have  been 
310  grains  (about  20  grammes),  not  allowing  for  an  in- 
creased quantity  demanded  to  supply  the  waste  engen- 
dered by  his  excessive  muscular  exertion.  He  had  dis- 
charged for  every  100  parts  of  nitrogen  introduced,  a  daily 
average  of  186.37  parts  for  four  days.  The  calculations, 
as  well  as  the  general  condition  of  the  system,  show  that 
the  period  had  probably  arrived  when  repair  of  the  mus- 
cular tissue  had  become  absolutely  necessary. 

If  these  facts  are  to  be  accepted — and  leaving  the  widest 
margin  for  inaccuracy  in  the  estimates,  they  can  not  in- 
volve any  considerable  error — it  is  difBcult  to  come  to  any 
other  conclusion  than  that  excessive  and  prolonged  mus- 
cular exercise  increases  largely  the  excretion  of  nitrogen, 
and  that  the  excess  of  nitrogen  discharged  is  due  to  an 
increased  disassimilation  of  the  muscular  substance;  and 
it  is  to  be  remembered  that  the  experiments  upon  which 
this  statement  is  based  were  made  with  a  diet  regulated 
entirely  by  the  wishes  of  the  person  under  observation. 

On  the  fifth  day,  after  9  hours  and  26  minutes  of  sleep, 
the  system  reacted  completely,  and  Weston  walked  forty 
and  a  half  miles.  The  nitrogen  of  the  urea  and  feces  was 
2i'}i2.'j'j  grains  (21.561  grammes).  The  nitrogen  of  the  food 
was  increased  165  per  cent.,  being  383.04  grains  (24.818 
grammes).  For  every  100  parts  of  nitrogen  of  food,  there 
were  discharged,  84.27  parts.  The  absolute  quantity  of 
nitrogen  discharged  was  still  very  great;  but  the  proportion 
to  the  nitrogen  introduced  was  reduced  by  the  large  quan- 
tity in  the  food. 

On  this  day,  when  there  was  apparent  reaction  after  the 
complete  prostration  of  the  fourth  day,  the  system  seemed 
to  appropriate  nitrogen  with  avidity,  to  repair  the  impov- 
erished muscular  tissue.  The  weight  was  increased  on  this 
day  by  28  oz.  (793  grammes). 

A  study  of  the  averages  for  the  five  days  of  this  period 
develops  points  of  much  importance,  some  of  which  have 


448  EXCRETION    OF    NITROGEN 

already  been  considered  in  connection  with  the  variations 
in  weight: 

I.  The  absokite  discharge  of  nitrogen  by  the  urea  and 
feces  for  each  day,  without  considering  the  nitrogen  of  the 
food,  is  in  a  nearly  uniform  proportion  to  the  number  of 
miles  walked.  This  proportion  is  but  little  disturbed  if  it 
is  assumed  that  the  influence  of  the  ingestion  of  nitrogen 
is  prolonged  for  a  period  of  twenty-four  to  forty-eight 
hours. 

II.  During  the  walk  of  317^  miles  in  five  consecutive 
days,  for  every  100  parts  of  nitrogen  taken  in  with  the 
food,  there  were  discharged  in  the  urea  and  feces,  153.99 
parts,  against  92.82  parts  per  100  for  the  five  days  before 
the  w-alk,  and  84.63  parts  per  100  for  the  five  days  after 
the  walk. 

III.  The  actual  loss  of  weight  during  the  five  days  of 
the  walk,  was  3.45  lbs.  (1,565.00  grammes).  The  total 
quantity  of  nitrogen  discharged  in  the  urea  and  feces  during 
this  period,  in  excess  of  the  nitrogen  taken  in  with  the 
food,  was  633.80  grains  (40.030  grammes).  Assuming  that 
3  parts  of  this  nitrogen  represent  the  waste  of  100  parts 
of  muscular  tissue,  the  loss  of  muscular  tissue  calculated 
from  the  nitrogen  excreted  would  be  3.018  lbs.  (1.334.33 
grammes),  leaving  only  0.43  of  a  pound  (230.67  grammes) 
unaccounted  for,  which  might  be  fat  or  water.* 

Third  Period,  Five  Days  after  the  Walk. — The 
record  of  the  fifth  day  of  the  second  period  shows  that  the 
system  had  already  begun  to  recuperate  after  the  depres- 
sion of  the  fourth  day,  notwithstanding  the  walk  of  forty 
and  a  half  miles.  The  explanation  of  this  is  to  be  found 
in  the  long  sleep  and  the  quantity  of  nitrogenous  food 
taken.  During  the  third  period  the  exercise  was  practically 
nothing,  being  only  2.2  miles  daily;  the  sleep  averaged  8 
hours  and  29  minutes;  and  the  nitrogen  of  the  food  aver- 
aged 440.93  grains  (28.569  grammes).  Weston  did  noth- 
ing but  eat,  sleep  and  amuse  himself,  and  this  w'as  a  period 
of  complete  bodily  and  mental  repose,  very  favorable  to 
recuperation  after  the  muscular  exertion  of  the  live  days 
before.  At  the  end  of  the  five  days  the  weight  had  in- 
creased to  120.75  lbs.  (54  k.  765  grammes),  0.25  of  a  pound 

*  See  the  section  on  variations  in  weight. 


EXCRETION   OF   NITROGEN  449 

(110.00  grammes)  above  the  weight  at  the  beginning  of  the 
observations.  Immediately  after  the  walk  Weston  felt 
perfectly  well  and  continued  well  for  the  five  days,  with  the 
exception  of  a  slight  headache  on  the  afternoon  and  even- 
ing of  the  fifth  day.  He  smoked  five  to  seven  cigars  daily, 
but  took  no  alcoholic  stimulants.  His  diet  was  normal  in 
variety,  but  on  some  days  the  quantity  of  solid  food  was 
very  large. 

On  the  first  day  the  nitrogen  of  the  food  was  385.65 
grains  (24.987  grammes),  about  64  per  cent,  above  the 
average  for  the  five  days  of  the  walk.  The  nitrogen  of  the 
urea  and  feces  was  295.70  grains  (19.159  grammes),  about 
18  per  cent,  below  the  average  for  the  five  days  of  the  walk. 
This  reduction  in  the  amount  of  nitrogen  excreted  is  sig- 
nificant. For  every  100  parts  of  nitrogen  of  food,  there 
were  discharged  in  the  urea  and  feces,  76.68  parts. 

On  the  second  day  the  nitrogen  of  the  food  was  much 
increased,  being  499.10  grains  (32.338  grammes).  The 
nitrogen  of  the  urea  and  feces  was  358.81  grains  (23.248 
grammes).  For  every  100  parts  of  nitrogen  of  food,  there 
were  discharged,  71.81  parts. 

On  the  third  day  the  nitrogen  of  the  food  was  dimin- 
ished, though  it  still  largely  exceeded  the  standard  for  a 
man  under  ordinary  conditions.  On  this  day  it  was  394.83 
grains  (25.582  grammes).  The  nitrogen  of  the  urea  and 
feces  was  largely  increased,  being  409.87  grains  (26.556 
grammes).  For  ever\'  100  parts  of  nitrogen  of  food,  there 
were  dischr^-ged,  103.81  parts.  This  excess  of  nitrogen 
discharged  is  to  be  attributed  to  the  large  quantity  of  nitro- 
gen taken  with  the  food  on  the  day  before. 

On  the  fourth  day  the  nitrogen  of  the  food  was  in  very 
large  quantity,  being  641.71  grains  (41.578  grammes), more 
than  double  the  average  for  a  man  under  ordinary  condi- 
tions. The  nitrogen  discharged  in  the  urea  and  feces  was 
382.89  grains  (24.808  grammes).  For  every  100  parts  of 
nitrogen  of  food,  there  were  discharged,  59.67  parts.  This 
proportion  was  reduced  by  the  very  large  quantity  of  nitro- 
gen taken  with  the  food. 

On  the  fifth  day  the  nitrogen  of  the  food  was  reduced 
to  a  little  below  the  average  for  a  man  under  ordinary  con- 
ditions, being  283.35  grains  (18.359  grammes).  The  nitro- 
gen   of   the    urea   and    feces    was   418.49    grains    (27.125 


450  EXCRETION   OF    NITROGEN 

grammes),  much  more  than  the  discharge  on  any  other 
day  of  the  fifteen.  For  every  lOO  parts  of  nitrogen  of 
food,  there  were  discharged,  147.69  parts.  This  active 
discharge  of  nitrogen  is  explained  by  the  large  amount 
taken  in  the  food  on  the  previous  day.  On  this  day,  at 
midnight,  the  observations  were  ended. 

The  daily  observations  during  this  period,  taken  in  con- 
nection with  those  during  the  five  days  before  the  walk, 
seem  to  establish  the  following  with  relation  to  the  influ-- 
ence  of  nitrogenous  food  on  the  excretion  of  nitrogen: 

Every  day  that  an  excess  of  nitrogenous  food  was  taken, 
it  was  followed,  on  the  succeeding  day,  and  on  one  occa- 
sion on  the  succeeding  two  days,  by  a  largely  increased 
discharge  of  nitrogen  in  the  urea  and  feces,  the  discharge 
on  these  days  exceeding  the  amount  taken  in  the  food;  but 
the  general  average  for  five  days,  during  the  period  of  five 
days  before  the  walk  and  the  period  of  five  days  after  the 
walk,  was  85  to  93  parts  of  nitrogen  discharged,  for  every 
100  parts  of  nitrogen  introduced. 

The  average  for  the  five  days  after  the  walk  shows  an 
introduction  of  440.93  grains  (28.569  grammes)  of  nitrogen 
daily,  an  excess  of  about  42  per  cent,  over  the  average  for 
a  man  under  ordinary  conditions.  For  every  100  parts  of 
nitrogen  in  the  food,  the  average  daily  excretion,  during 
this  period,  was  84.63  parts. 

INFLUENCE     OF     EXERCISE     UPON     THE     ELIMINATION     OF 

URIC   ACID 

The  results  of  the  observations  during  the  three  periods, 
as  regards  the  influence  of  the  exercise  during  the  five 
days  of  the  walk  and  the  influence  of  food  during  the  five 
days  before  and  the  five  days  after  the  walk,  are  unsatis- 
factory and  are  interesting  chiefly  from  a  negative  point  of 
view. 

The  quantities  of  uric  acid  for  each  day  present  very 
wide  variations.  For  example,  on  the  fourth  day  of  the 
walk,  the  exercise  being  fifty-seven  miles,  the  quantity  was 
9.21  grains  (0.597  of  a  gramme),  the  greatest  amount  for 
any  one  day;  and  on  the  second  day  of  the  walk,  the  exer- 
cise being  forty-eight  miles,  the  uric  acid  was  0.14  of  a 
grain  (0.009  o^  ^  gramme) ;  the  smallest  amount  for  any  one 


EXCRETION    OF    NITROGEN  451 

day.  On  the  second  day  of  the  first  period  the  quantity 
was  4.03  grains  (0.261  of  a  gramme);  and  on  the  third  day 
after  the  walk  the  quantity  was  0.31  of  a  grain  (0.02  of  a 
gramme).  I  have  carefully  compared  the  quantities  for  each 
day  with  the  exercise  and  can  find  no  definite  relation  be- 
tween them.  I  have  also  carefully  compared  the  quantities 
for  each  day  with  the  character  and  quantity  of  food,  but 
with  no  more  satisfactory  result.  Inasmuch  as  on  certain 
days  during  the  walk  Weston  took  large  quantities  of  cof- 
fee, it  occurred  to  me  that  this  might  influence  the  uric 
acid;  but  I  did  not  find  any  confirmation  of  this  in  the  tables. 
I  calculated  also  for  each  day  the  proportion  of  uric  acid  per 
100  parts  of  urea  discharged,  with  the  view  of  confirming 
or  disproving  the  idea  that  uric  acid  represents  urea  in  an 
imperfect  condition  of  oxidation;  but  the  results  of  these 
calculations  were  also  unsatisfactory.  Finally  I  compared 
the  sleep  and  the  meteorological  record  with  the  uric  acid 
and  could  establish  no  relation  between  them.  The  varia- 
tions were  so  irregular  that  it  was  impossible  to  trace  any 
influence  upon  the  uric  acid  due  to  food  or  exercise,  even 
if  it  is  assumed  that  the  influence  might  be  protracted  for 
a  period  of  one  or  more  days. 

As  it  is  impossible  to  draw  any  positive  conclusions 
from  a  comparison  of  the  quantities  of  uric  acid  excreted 
day  by  day,  I  can  only  refer  to  the  averages  for  the  three 
periods  of  five  days  each. 

The  average  daily  excretion  of  uric  acid  for  the  five 
days  before  the  walk  was  2.26  grains  (0.127  of  a  gramme). 
The  proportion  of  uric  acid  per  100  parts  of  urea  for  this 
period  was  0.360  of  a  part. 

The  average  daily  excretion  for  the  five  days,  walking 
in  all  317^  miles,  was  3  grains  (0.194  of  a  gramme).  The 
proportion  of  uric  acid  per  100  parts  of  urea  for  this  period 
was  0.415  of  a  part. 

The  average  daily  excretion  for  the  five  days,  walking 
walk  was  1.42  grains  (0.082  of  a  gramme).  The  proportion 
of  uric  acid  per  100  parts  of  urea  for  this  period  was  0.195 
of  a  part. 

These  results,  in  view  of  the  unexplained  daily  varia- 
tions in  the  uric  acid,  are  not  sufficiently  definite  to  lead 
to  any  positive  conclusions.  So  far  as  they  go,  they  show 
an  increase  in  the  uric  acid  of  about  33  per  cent,  during 


452  EXCRETION   OF   NITROGEN 

the  period  of  extraordinary  muscular  exertion.  During 
the  period  of  complete  muscular  inactivity,  with  an  excess 
of  food,  the  excretion  was  diminished  by  about  one-half. 
The  observations  have  developed,  however,  the  follow- 
ing negative  facts: 

I.  There  was  no  apparent  relation  between  the  increase 
of  urea  and  of  uric  acid,  except  that  both  were  increased, 
with  the  other  solid  constituents  of  the  urine.  In  other 
words,  in  increasing  the  urea  by  exercise,  there  is  no  evi- 
dence that  uric  acid  is  oxidized  and  converted  into  urea; 
for  if  that  had  been  the  case,  with  the  increase  in  the  quan- 
tity of  urea,  there  would  have  been  a  diminution  in  the 
proportion  of  uric  acid  per  lOO  parts  of  urea;  and  this  did 
not  occur. 

II.  It  was  not  shown  that  the  quantity  of  nitrogenous- 
food  has  any  influence  upon  the  elimination  of  uric  acid; 
unless  it  be  assumed  that  the  diminution  in  the  uric  acid, 
during  the  period  of  inactivity  and  excess  of  nitrogenous 
food,  was  due  to  the  food  alone. 

The  important  physiological  results  which  I  hoped  to 
arrive  at  by  studying  the  uric  acid,  with  the  applications 
of  such  results  to  pathological  conditions,  were  not  real- 
ized; and  it  must  be  admitted  that  positive  knowledge  of 
the  relations  of  uric  acid  to  nutrition  and  disassimilation 
has  not  been  advanced  by  these  researches,  although  some 
important  negative  facts  have  been  developed. 

IXFLUEXCE     OF     EXERCISE     UPON     THE     ELIMINATION     OF 
INORGANIC    SALTS    BY    THE    KIDNEYS 

In  Studying  the  variations  in  the  proportions  of  inor- 
ganic salts  in  the  urine,  it  will  be  seen  that  the  phosphoric 
and  the  sulphuric  acid  are  generally  in  about  the  same  ratio 
to  each  other,  their  excretion  being  apparently  increased 
and  diminished  by  the  same  causes.  With  the  chloride  of 
sodium,  however,  it  is  dififerent.  For  example,  on  the  third 
day  of  the  walk  the  quantity  of  phosphoric  acid  was  large, 
while  the  chloride  of  sodium  was  in  very  small  quantity, 
nearly  at  the  minimum.  As  it  is  not  improbable  that  differ- 
ent causes  may  influence,  on  the  one  hand,  the  phosphoric 
and  the  sulphuric  acid,  and  on  the  other,  the  chloride  of 
sodium,  it  will  be  proper  to  consider  the  chloride  by  itself. 


EXCRETION    OF    NITROGEN  453 

Phosphoric  and  Sulphuric  Acid. — It  is  undoubted- 
ly true  that  the  excretion  of  the  phosphates  and  sulphates 
by  the  kidneys  is  largely  influenced  by  the  quantity  of 
these  salts  in  the  food.  They  must,  however,  pass  into  the 
urine  in  one  or  both  of  two  ways;  either  directly  from  the 
blood,  the  salts  being  taken  up  by  absorption  without  be- 
coming a  part  of  the  tissues,  or  they  may  come  from  the 
tissues,  by  a  process  analogous  to  that  of  the  production 
of  urea.  If  these  salts  passed  directly  from  the  blood,  their 
elimination  would  be  almost  entirely  under  the  influence  of 
the  food;  and  this  influence  would  be  apparent  soon  after 
their  introduction.  If  the  phosphates  and  sulphates  of  the 
urine  are  derived  from  the  tissues  in  the  process  of  disas- 
similation,  when  this  process  is  increased  in  activity,  as  it 
was  during  the  five  days  of  the  walk,  the  influence  of  the 
food  would  probably  be  overshadowed  by  the  exaggerated 
activity  of  disassimilation,  due  to  the  extraordinary  mus- 
cular work.  It  is  not  possible  to  subject  these  questions 
to  rigidly  scientific  inquiry  without  estimating  exactly  the 
phosphoric  and  the  sulphuric  acid  in  the  food.  This  was 
impracticable;  but  the  solid  food  was  so  little  changed  in 
its  character  during  the  different  days  of  the  three  periods, 
that  the  variations  in  its  quantity  will  be  to  a  certain  extent 
a  measure  of  the  introduction  of  the  inorganic  salts. 

First  Period,  Five  Days  before  the  Walk. — Dur- 
ing this  period  the  range  of  variation  from  day  to  day  was 
between  43.01  and  67.00  for  the  phosphoric  acid,  and  be- 
tween 38.18  and  51.50  for  the  sulphuric  acid.  With  one 
exception,  these  two  acids  varied  from  day  to  day  in  about 
the  same  ratio.  On  the  first  day  the  phosphoric  acid  was 
in  large  quantity,  with  a  small  quantity  of  sulphuric  acid. 
With  the  exception  of  the  fifth  day  both  the  phosphoric 
and  the  sulphuric  acid  were  varied  in  a  nearly  constant 
ratio  to  the  variations  in  the  nitrogenous  food,  being  in- 
creased with  the  food  and  rice  versa.  On  the  fifth  day, 
when  the  quantity  of  nitrogenous  food  was  the  greatest, 
both  the  phosphoric  and  the  sulphuric  acid  were  below  the 
average  for  the  five  days.  On  this  day  the  exercise  was 
very  little,  only  one  mile. 

The  most  marked  and  constant  variations  during  this 
period  were  with  the  exercise,  especially  in  the  phosphoric 
acid.     On  the  first  day  the  exercise  was  fifteen  miles;  the 


454  EXCRETION   OF    NITROGEN 

phosphoric  acid  was  51.46  grains  (3-334  grammes),  the 
average  for  the  five  days  being  50.14  grains  (3.262 
grammes),  and  the  sulphuric  acid  was  38.37  grains  (2.486 
grammes),  the  average  being  41.57  grains  (2.693  grammes). 
On  the  fourth  day  the  exercise  was  fifteen  miles;  the  phos- 
phoric acid  was  67  grains  (4.341  grammes),  and  the  sul- 
phuric acid,  51.50  grains  (3.337  grammes).  On  this  day 
the  loss  of  weight  w-as  24  oz.  (687  grammes),  the  greatest 
loss  for  any  one  of  the  five  days.  On  the  second  and  third 
days  both  the  phosphoric  and  the  sulphuric  acid  were 
slightly  below  the  average  for  the  five  days,  with  five  miles 
of  exercise  each  day.  On  the  fifth  day,  with  ten  hours  of 
sleep  and  one  mile  of  exercise,  the  phosphoric  acid  was 
43.01  grains  (2.787  grammes),  and  the  sulphuric  acid,  38.18 
grains  (2.474  grammes),  the  smallest  quantities  during  the 
five  days. 

During  this  period  the  increase  in  the  phosphoric  and 
the  sulphuric  acid  with  the  exercise  w^as  constant. 

Second  Period,  Five  Days  of  the  Walk. — During 
this  period  the  ratio  of  variations  between  the  phosphoric 
and  the  sulphuric  acid  w-as  constant,  with  the  exception  of 
the  fifth  day,  when  the  quantity  of  sulphuric  acid  was  a 
little  greater  than  on  the  fourth  day,  wdiile  the  phosphoric 
acid  was  less.  During  this  period  there  was  no  definite 
relation  between  the  quantities  of  these  two  acids  and  the 
nitrogenous  food;  the  influence  of  the  food  being  appar- 
ently overshadowed  by  the  exercise.  The  relations  be- 
tween the  phosphoric  acid  and  the  exercise  were  nearly 
absolute.  Taking  the  exercise  from  the  highest  to  the 
lowest  points,  the  relations  were  as  follows: 


Third  day. 
First  day. 
Fourth  day. 
Second  day. 
Fifth  day. 

Exercise 

92  miles. 
80      " 

57      " 
48      " 
4oi    " 

H3PO4 

102.25 

84.95 
66.90 

72.14 

57.49 

grains  (6.625 

"       (5504 
(4.296 

"       (4674 
"       (3.725 

gram 

mes). 
). 
)- 
). 
). 

The  variations  in 

the  sulphuric  acid  were  not 

so  regular : 

Third  day. 
First  day. 
Fourth  day. 
Second  day. 
Fifth  day. 

Exercise 

92  miles. 
80      " 

57      " 
48      " 
40^^    " 

H.SO4 

63.71 

73-39 
32.66 
56.90 
40.84 

grains  (4.128 

"      (4-755 
"      (2.1 16 
"      (3.687 
"      (2.646 

gram 

mes). 
). 
). 
). 
). 

These  calculations  show  a  decided  and  nearly  absolute 
relation  between  the  excretion  of  phosphoric  acid  and  the 


EXCRETION   OF   NITROGEN  455 

exercise.  On  the  fourth  day,  with  fifty-seven  miles  of  exer- 
cise, the  nitrogen  of  the  food  was  about  forty-six  per  cent, 
less  than  on  the  second  day,  with  forty-eight  miles  of  exer- 
cise. This  will  perhaps  account  for  the  diminished  excre- 
tion during  the  day  of  less  exercise. 

As  regards  sulphuric  acid,  the  conclusions  are  about 
the  same  as  for  phosphoric  acid.  The  diminished  excre- 
tion on  the  second  day  is  also  accounted  for  by  the  small 
quantity  of  nitrogenous  food  taken  on  that  day. 

Third  Period,  Five  Days  after  the  AValk. — Dur- 
ing this  period  the  exercise  was  practically  nothing;  and 
this  element  does  not,  therefore,  enter  into  the  calcu- 
lation of  the  variations  of  the  inorganic  constituents  of 
the  urine.  Although  the  variations  in  the  phosphoric 
and  the  sulphuric  acid  were  considerable,  as  were  the 
daily  variations  in  the  nitrogenous  food,  there  seemed 
to  be  no  definite  relation  between  them.  I  shall  there- 
fore give  for  this  period  simply  the  extremes  and  the 
averages. 

On  the  third  day  the  quantities  both  of  phosphoric  and 
of  sulphuric  acid  were  the  greatest.  The  phosphoric  acid 
was  105.68  grains  (6.847  grammes).  The  sulphuric  acid 
was  53.57  grains  (3.471  grammes).  On  the  first  day  the 
phosphoric  acid  was  least  in  quantity,  being  29.06  grains 
(1.833  grammes),  with  49.53  grains  (3.209  grammes)  of 
sulphuric  acid.  On  the  second  day  the  sulphuric  acid  was 
least  in  quantity,  being  46.07  grains  (2.985  grammes),  with 
46.93  grains  (3.041  grammes)  of  phosphoric  acid. 

The  averages  for  the  five  days  of  this  period  were  as 
follows:  Phosphoric  acid,  56.89  grains  (3.674  grammes); 
sulphuric  acid,  49.02  grains  (3.176  grammes). 

Averages  for  the  Three  Periods. — The  averages 
for  the  three  periods  of  five  days  each  show  the  influence 
of  exercise  upon  the  elimination  of  phosphoric  and  sul- 
phuric acid;  and  the  averages  for  the  period  of  five  days 
before  the  walk  and  the  period  of  five  days  after  the  walk 
show  the  influence  of  food,  probably  attributable  to  the 
phosphates  and  sulphates  combined  with  the  nitrogenous 
matters. 

For  the  first  period,  five  days  before  the  walk,  the  aver- 
age discharge  of  phosphoric  acid  was  50.14  grains  (3.262 
grammes),    and    of    sulphuric    acid,    41.57    grains    (2.693 


456  EXCRETION    OF    NITROGEN 

grammes).  The  average  quantity  of  nitrogen  in  the  food 
was  339.46  grains  (21.994  grammes). 

For  the  second  period,  five  days  of  the  walk,  the  aver- 
age discharge  of  phosphoric  acid  was  76.63  grains  (4-965 
grammes),  and  of  sulphuric  acid,  53.50  grams  (3.666 
grammes).  The  average  quantity  of  nitrogen  in  the  food 
was  234.76  grains  (13.21 1  grammes). 

For  the  third  period,  five  days  after  the  walk,  the  aver- 
age discharge  of  phosphoric  acid  was  56.89  grains  (3.674 
grammes),  and  of  sulphuric  acid,  49.02  grains  (3.176 
grammes).  The  average  quantity  of  nitrogen  in  the  food 
was  440.93  grains  (28.569  grammes). 

These  averages  show  that  the  walk  of  317^  miles  in 
five  consecutive  days  increased  the  excretion  of  phosphoric 
acid  more  than  50  per  cent,  over  the  excretion  under  ordi- 
nary conditions,  notwithstanding  that  the  nitrogenous  food 
was  diminished  31  per  cent.  Under  the  same  conditions 
there  was  an  increase  of  about  30  per  cent,  in  the  excretion 
of  sulphuric  acid.  The  influence  of  exercise  upon  the  ex- 
cretion of  the  phosphates  and  sulphates,  irrespective  of  the 
composition  of  the  food,  can  hardly  be  doubted. 

A  comparison  of  the  averages  for  the  first  period,  five 
days  before  the  walk,  and  the  third  period,  five  days  after 
the  walk,  shows  an  increase  in  the  excretion  of  phosphoric 
acid,  for  the  third  period,  of  13.4  per  cent.,  with  an  increase 
of  30  per  cent,  in  the  quantity  of  nitrogenous  food.  Under 
the  same  conditions  the  excretion  of  sulphuric  acid  was  in- 
creased by  19.2  per  cent. 

Chloride  of  Sodium. — In  the  absence  of  exact  esti- 
mates of  the  quantities  of  chloride  of  sodium  contained  in 
the  food  of  each  day,  there  is  little  to  be  learned  from  the 
variations  in  excretion  of  this  salt  by  the  kidneys.  Such 
estimates  were  manifestly  impracticable.  The  salt  used  as 
a  condiment  was  averaged  for  the  four  days  of  the  first 
period  and  for  the  fifth  day  of  this  period,  with  the  five 
days  of  the  walk.  For  the  five  days  after  the  walk  the 
quantity  of  salt  used  was  weighed  each  day.  I  can  form 
no  definite  idea  of  the  salt  used  in  cooking  for  the  five  days 
before  the  walk  and  the  five  days  after  the  walk;  but  on 
some  of  the  days  of  the  walk,  particularly  the  third  and 
fourth,  the  diet  consisted  largely  of  beef-essence  and  oat- 
meal-gruel.    No  salt  was  added  to  the  beef-essence,  which 


EXCRETION    OF    NITROGEN  457. 

was  prepared  under  my  own  direction,  and  very  little  was 
used  in  the  preparation  of  the  oatmeal-gruel. 

First  Period,  Five  Days  before  the  Walk. — The 
average  quantity  of  salt  used  as  a  condiment  during  this 
period  was  34.5  grains  (2.235  grammes).  During  the  tive 
days  the  proportion  of  nitrogenous  food  and  the  elimina- 
tion of  chloride  of  sodium  presented  no  definite  relation 
to  each  other.  The  variations  in  the  chloride  of  sodium 
of  the  urine  were  not  considerable  and  had  no  definite 
relation  to  the  exercise.  The  greatest  quantity  was  on  the 
first  day.  being  195.02  grains  (12.636  grammes);  and  the 
smallest  quantity  was  on  the  fourth  day,  when  it  was  106.68 
grains  (6.912  grammes).  In  the  absence  of  any  definite 
relation  between  the  excretion  of  chloride  of  sodium  and 
either  the  food  or  the  exercise,  I  can  use  only  the  average 
for  this  period,  which  was  159.45  grains  (10.331  grammes). 

Second  Period,  Five  Days  of  the  Walk. — There 
are  some  interesting  points  connected  with  the  elimina- 
tion of  chloride  of  sodium  during  this  period.  The  ni- 
trogenous food,  which  contained  nearly  all  the  chloride  of 
sodium,  was  diminished  by  31  per  cent.,  and  the  average 
quantity  of  salt  used  as  a  condiment  was  35  grains  (2.265 
grammes).  The  average  elimination  of  chloride  of  sodium 
by  the  kidneys  was  only  65.08  grains  (4.217  grammes); 
but  a  large  quantity  must  have  been  eliminated  by  the  skin, 
the  average  cutaneous  and  pulmonary  exhalation  daily 
being  138.41  oz.  (3,875.18  grammes),  against  61.63  oz. 
{1,690.91  grammes)  for  the  five  days  before  the  walk,  and 
62.82  oz.  (1,706.78  grammes)  for  the  five  days  after  the 
walk. 

On  the  third  day,  when  the  food  contained  probably 
the  minimum  proportion  of  salt,  the  salt  of  the  urine  was 
reduced  to  44.45  grains  (2.88  grammes),  about  32  per  cent, 
below  the  average  for  the  five  days.  On  the  fourth  day 
it  is  probable  that  a  little  more  salt  was  taken  with  the  food. 
On  this  day  the  exercise  was  fifty-seven  miles;  but  it  was 
on  this  day  that  W^eston  broke  down  and  was  forced  to 
take  a  long  rest.  The  chloride  of  sodium  for  this  day  was 
reduced  to  28.78  grains  (1.865  gramme),  nearly  56  per 
cent,  below  the  average.  On  the  next  day,  when  reaction 
took  place,  the  salt  returned  to  about  the  average.  In 
A-iew  of  the  disappearance  of  the  chloride  of  sodium  of  the 
30 


4S8  EXCRETION   OF   NITROGEN 

urine  in  certain  febrile  conditions,  this  diminution  in  its 
quantity  on  the  day  of  great  constitutional  depression 
is  interesting,  although  its  exact  significance  is  not  ap- 
parent. 

Third  Period,  Five  Days  after  the  Walk. — The 
variations  in  the  chloride  of  sodium  of  the  urine  during 
this  period  were  very  great.  The  smallest  quantity  was 
on  the  first  day,  when  it  was  66.41  grains  (4.303  grammes). 
The  largest  quantity  was  on  the  third  day,  when  it  w'as 
622.58  grains  (40.338  grammes).  The  quantity  of  urine 
on  this  day  was  84.18  fi  .")  (2,490  cc).  I  could  not  connect 
these  variations  either  with  the  diet  or  with  the  salt  used 
as  a  condiment,  which  was  weighed  each  day  and  varied 
considerably.  The  only  point  connected  with  the  daily 
variations  during  this  period  is  the  small  quantity  on  the 
day  next  after  the  walk,  when  it  w^as  only  66.41  grains 
(4.303  grammes),  while  the  salt  actually  used  as  a  condi- 
ment on  that  day  was  65.62  grains  (4.252  grammes). 

The  average  daily  quantity  of  chloride  of  sodium  of  the 
urine  for  this  period  was  312.40  grains  (20.241  grammes). 
The  nitrogenous  food  was  increased  by  30  per  cent,  over 
the  average  for  the  five  days  before  the  w-alk.  The  average 
quantity  of  salt  used  as  a  condiment  was  42  grains  (2.721 
grammes),  an  increase  of  nearly  22  per  cent,  over  the  aver- 
age for  the  five  days  before  the  w-alk. 

Averages  for  the  Three  Periods. — The  averages 
for  the  three  periods  of  five  days  each  are  as  follows: 

First  period,  five  days  before  the  walk;  159.45  grains 
(10.331  grammes). 

Second  period,  five  days  of  the  walk,  65.08  grains  (4.217 
grammes). 

Third  period,  five  days  after  the  walk.  312.40  grains 
(20.241  grammes). 

These  averages  show  a  great  diminution  in  the  chloride 
of  sodium  of  the  urine  during  the  walk,  due  in  a  great 
measure,  undoubtedly,  to  a  diminution  in  the  quantity  of 
salt  ingested.  In  the  absence  of  exact  estimates  of  the 
quantity  of  salt  introduced,  it  is  impossible  to  state  defi- 
nitely the  influence  of  exercise  on  its  elimination  by  the 
kidneys.  Probably  it  is  diminished,  a  much  larger  quantity 
than  usual  being  eliminated  by  the  skin.  An  argument 
in  favor  of  this  view  is  the  small  quantity  in  the  urine  the 


EXCRETION   OF   NITROGEN  459 

day  next  after  the  walk,  when  a  large  quantity  was  intro- 
duced with  the  food. 

The  only  explanation  I  can  offer  of  the  great  increase 
in  the  chloride  of  sodium  during  the  five  days  after  the 
walk  is  in  the  larger  quantity  taken  with  the  food,  and 
possibly  the  cessation  of  the  influences  which  diminished 
it  in  the  urine  during  the  five  days  of  the  walk. 

ABNORMAL    MATTERS    IN    THE    URINE 

There  is  very  little  to  be  said  in  regard  to  the  abnormal 
'matters  discovered  by  microscopical  examination  of  the 
urinary  sediments.  During  the  first  period,  five  days  be- 
fore the  walk,  there  was  a  constant  deposit  of  octahedra 
of  oxalate  of  lime.  During  the  second  period,  five  days 
of  the  walk,  oxalate  of  lime  was  found  daily.  On  the  fifth 
day  of  this  period,  in  addition  to  oxalate  of  lime,  there 
was  a  small  quantity  of  the  amorphous  phosphates.  The 
oxalate  of  lime  continued  during  the  third  period,  five 
days  after  the  walk,  with  the  exception  of  the  fourth  day, 
when  there  were  no  abnormal  matters.  On  the  first  day 
of  this  period  the  sediment  contained,  in  addition  to  oxa- 
late of  lime,  amorphous  urates  in  small  quantity.  On  the 
second  and  the  third  day  of  this  period,  in  addition  to 
oxalate  of  lime,  the  sediment  contained  crystals  of  uric 
acid.  On  these  days  the  quantity  of  uric  acid  in  the  urine, 
determined  by  analysis,  was  very  small,  and  the  crystals 
were  probably  due  to  increased  acidity  of  the  urine.  I  can 
ofifer  no  explanation  of  the  presence  of  any  of  these  crystals 
in  the  urine  nor  can  I  connect  them  with  any  of  the  con- 
ditions observed. 

On  the  second  and  the  third  day  of  the  third  period, 
five  days  after  the  walk,  the  urine  contained  a  trace  of  sugar. 
There  was  no  increase  in  the  quantities  of  starchy  and 
saccharine  matters  in  the  food  on  these  days  to  account 
for  the  sugar,  the  presence  of  which  can  not  readily  be 
explained. 

In  conclusion,  it  is  evident,  from  the  results  of  these 
investigations,  that  the  question  of  the  influence  of  muscu- 
lar exercise  upon  the  elimination  of  nitrogen  can  be  accu- 
rately studied  only  by  comparing  the  nitrogen  of  the  food 
with  the  nitrogen  of  the  excretions;  and  this  should  be  done 


46o  EXCRETION   OF  NITROGEN 

if  possible  upon  a  perfectly  physiological  diet.  It  is  indis- 
pensable, also,  to  extend  the  experiments  over  periods  of 
several  days  each;  otherwise  the  results  will  necessarily  be 
confused  and  unsatisfactory.  The  observations  in  regard 
to  the  body-weight  and  various  other  conditions  were 
necessary  to  control  the  more  important  points  to  be  con- 
sidered. The  great  amount  of  material  collected  and  its 
analysis  and  tabulation  have  involved  considerable  labor, 
which,  however,  has  been  rewarded  by  important  conclu- 
sions of  a  definite  and  positive  character. 

At  the  risk  of  presenting  to  the  reader  an  unattractive 
mass  of  statistics,  I  have  thought  it  proper  to  publish,  not 
only  the  general  facts  and  deductions,  but  the  exact  data 
collected,  arranged  in  a  form  that  may  be  useful  to  other 
investigators.  I  feel  confident  that  I  shall  not  be  re- 
proached for  tediousness  of  detail  by  those  who  are  inter- 
ested in  the  important  physiological  questions  involved, 
particularly  those  who  have  carefully  studied  the  literature 
of  these  questions  for  the  past  few^  years. 


XX 

SUPPLEMENTARY  REMARKS  "ON  THE  EF- 
FECTS OF  SEVERE  AND  PROTRACTED 
MUSCULAR  EXERCISE;  WITH  SPECIAL 
REFERENCE  TO  ITS  INFLUENCE  ON  THE 
EXCRETION   OF  NITROGEN" 

Published  in  the  "  Journal  of  Anatomy  and  Physiology,"  Cambridge  and 
London,  for  October,  1876. 

In  June,  1871  I  published  in  the  "  New  York  IMedical 
Journal  "  an  account  of  a  series  of  observations  made  upon 
Weston,  the  pedestrian,  during  one  of  his  feats  of  endur- 
ance. My  researches  have  lately  been  in  part  repeated  and 
confirmed  in  England  by  Dr.  Pavy.  My  original  observa- 
tions were  made  with  the  utmost  care,  and  they  involved 
a  great  deal  of  labor.  They  were  most  decidedly  opposed, 
in  their  results,  to  the  modern  view  regarding  the  influence 
of  muscular  exercise  on  the  excretion  of  urea,  which  is 
based  upon  the  experiments  of  Fick  and  Wislicenus,  made 
in  1866,  and  upon  other  observations  apparently  confirma- 
tory of  the  notion  that  the  elimination  of  urea  is  not  in- 
creased by  muscular  work.  This  view  I  believe  to  be  in- 
correct; and  I  regard  the  experiments  upon  which  it  rests 
as  imperfect,  faulty  and  made  under  unphysiological  con- 
ditions. 

The  question  of  the  influence  of  muscular  exercise  on 
the  elimination  of  nitrogen  being  of  great  importance  in 
its  pathological  as  well  as  in  its  physiological  relations, 
it  was  to  be  expected  that  conclusions  opposed  to  the 
generally-accepted  ideas,  even  when  deduced  from  very 
extended  experiments,  would  be  viewed  with  distrust 
and  receive  adverse  criticism.  I  have  not  failed  to  real- 
ize this  expectation;  although  it  seemed  to  me  that  my 
conclusions  could  not  be  successfully  controverted  with- 

461 


462  EXCRETION    OF    NITROGEN 

out  a  denial  of  the  accuracy  of  my  experimental  data. 
I  shall  here  refer  only  to  the  criticisms  of  Dr.  Pavy, 
as  he  is  now  the  one  physiologist  who  is  in  a  position 
to  judge,  from  his  own  knowledge,  of  the  reliability 
of  my  observations.  These  criticisms,  however,  seem  to 
me  to  be  general  rather  than  definite  and  positive.  They 
are  summed  up  substantially  in  the  following  para- 
graph, quoted  from  Dr.  Pavy's  work  on  "  Food  and 
Dietetics  ": — 

"  Now,  apart  from  the  fact  that  a  marked  deviation  from  the 
physiological  state  existed  when  the  results  upon  which  the  con- 
clusions are  based  were  yielded,  is  there  anything  in  the  results 
to  show  that  in  reality  we  have  more  to  deal  with  than  simply  a 
consumption  of  nitrogenous  material  within  the  system  beyond  the 
supply  for  the  time  from  without?  Taking  the  figures  throughout, 
there  is  not  much  more  to  be  seen  than  a  difference  occasioned  by  a 
falling  off  in  the  amount  of  nitrogen  ingested  during  the  first  four 
days  of  the  walk ;  and  it  is  well  known  that  when  the  ingesta  do 
not  furnish  what  is  wanted  for  meeting  the  expenditure  going  on 
(as  during  inanition),  the  resources  of  the  body  are  drawn  upon, 
and  the  nitrogenous  matter  existing  in  the  various  parts — both 
solids  and  fluids — wastes  or  yields  itself  up  as  well  as  the  rest.  On 
the  fifth  day,  after  a  prolonged  sleep,  which  appears  to  have  re- 
stored the  flagging  powers,  the  previous  relation  was  reversed. 
The  food  ingested  afforded  more  than  enough  to  meet  the  require- 
ments. There  was  a  gain  of  if  pound  in  body- weight,  and  accord- 
ing to  the  figures,  the  nitrogen  discharged  fell  short  by  50.27  grains 
of  that  which  entered,  notwithstanding  a  walk  of  forty  miles  and 
a  half  was  performed."  * 

This  paragraph,  without  a  knowledge  of  the  details  of 
my  experiments,  may  seem  obscure.  I  think  Dr.  Pavy 
intended  to  reason  as  follows: — Although  I  had  demon- 
strated, for  the  first  four  days  of  a  feat  performed  by  Wes- 
ton in  which  he  had  walked,  the  first  day  80  miles,  the  sec- 
ond day  48  miles,  the  third  day  92  miles  and  the  fourth  day 
57  miles,  that  there  was  a  large  increase  in  the  nitrogen 
excreted  over  the  nitrogen  of  food,  it  is  assumed  by  Dr. 
Pavy  that  this  apparent  excess  was  due  to  a  deficient  inges- 
tion of  nitrogen  and  not  necessarily  to  an  increase  in  the 
excretion  of  nitrogen.  The  fact  is  that  comparing  four 
days,  during  which  277  miles  were  walked,  with  four  days 
before,  during  which  26  miles  were  w^alked,  in  four  days, 

*  Pavy,  "  Food  and  Dietetics,"  Philadelphia,  1874,  p.  71. 


EXCRETION    OF    NITROGEN  463 

walking  26  miles,  there  were  1,336.06  grains  of  nitrogen 
in  the  food,  against  790.78  grains  during  four  days,  walk- 
ing 277  miles,  or  a  deficiency  in  the  nitrogen  of  food  dur- 
ing the  latter  period  of  545.28  grains.  During  the  four 
days,  walking  26  miles,  the  nitrogen  excreted  was  1,252.17 
grains,  against  1,473.85  grains  during  the  four  days,  walk- 
ing ^yy  miles,  or  an  excess  of  nitrogen  excreted  of  221.68 
grains.  It  is  evident  that  the  excessive  exertion  of  walk- 
ing 277  miles  in  four  consecutive  days  induced  an  increase 
in  the  excretion  of  nitrogen;  not  only  sufificient  to  equal 
the  deficiency  of  the  nitrogen  of  food,  but  a  considerable 
excess.  The  excess  of  the  nitrogen  excreted  during  the 
four  days,  walking  277  miles,  over  the  four  days,  walking 
26  miles,  irrespective  of  the  nitrogen  ingested,  was  221.68 
grains;  and  the  excess  of  nitrogen  excreted  during  the  four 
days,  walking  277  miles,  over  the  nitrogen  ingested  dur- 
ing the  four  days,  walking  26  miles,  was  137.79  grains.  It 
seems  to  me  that  the  figures  and  deductions  which  I  gave 
in  my  original  article,  in  which  I  show  the  effects  of  pro- 
longed and  severe  muscular  exercise  on  the  excretion  of 
nitrogen,  not  only  in  absolute  quantity  but  in  proportion 
to  the  nitrogen  ingested,  are  sufficiently  clear  and  distinct; 
and  the  complications  in  these  deductions,  if  they  exist, 
are  due  to  the  process  of  reasoning  from  my  figures  em- 
ployed by  Dr.  Pavy.  It  does  not  appear  that  any  physi- 
ological demonstration  could  be  more  positive  than  that 
of  the  proposition  that  muscular  exercise  increases,  not 
only  the  absolute  quantity  of  nitrogen  excreted,  but  the 
proportionate  quantity  of  nitrogen  eliminated  to  the 
nitrogen  of  food. 

My  first  impression,  in  studying  the  experiments  of  Fick 
and  Wislicenus,  was  that  the  observations  on  the  influence 
of  exercise  upon  the  elimination  of  nitrogen  were  made 
upon  a  purely  non-nitrogenous  diet  on  account  of  the  labor 
and  difficulty  attending  an  accurate  estimation  of  the  nitro- 
gen of  food;  but  it  now  seems  to  me  that  this  was  not  the 
only  idea  under  which  this  method  of  experimentation  was 
adopted.  It  is  a  seductive,  and  was  a  more  or  less  novel 
idea,  that  the  animal  organism,  after  it  has  become  fully 
developed,  is  a  machine  which  consumes  food  as  fuel,  and 
that  it  does  not  constantly  wear  out  its  own  substance  by 
work  and  repair  itself  by  the  ingesta.     With  this  view,  it 


464  EXCRETION   OF   NITROGEN 

would  seem  possil)Ie  to  reduce  the  values  of  food  to 
mathematical  accuracy,  calculating  the  heat-units,  foot- 
pounds, etc.,  of  various  articles  of  diet.  Such  calculations 
would  be  very  indefinite  for  any  restricted  period  of  time, 
adopting  the  view  that  the  nitrogenous  constituents  of  the 
body  wear  and  are  consumed  with  muscular  work  and  that 
they  are  regenerated  by  the  nitrogenous  matters  of  food. 
A  necessary  basis  for  an  accurate  estimation  of  heat  and 
work-units  of  food  is  the  idea  that  food  is  directly  con- 
sumed in  the  production  of  heat  and  in  work.  While  cal- 
culations of  these  units  with  mathematical  accuracy  would 
be  very  desirable  as  giving  definite  form  to  ideas  of  the 
value  of  food,  they  still  want  a  positive  basis  in  fact.  In 
carrying  out  this  idea,  it  seems  to  me  that  the  value  of 
many  of  the  experiments  is  made  to  depend  on  the  assump- 
tion of  the  truth  of  the  proposition  which  they  are  in- 
tended to  support. 

In  view  of  the  importance  of  the  results  obtained  by 
me,  and,  as  I  believe,  confirmed  by  the  recent  observations 
of  Dr.  Pavy,  it  would  be  interesting  to  assimilate  and  com- 
pare the  two  sets  of  observations,  the  more  so  as  I  could 
scarcely  have  hoped  that  independent  researches  would 
have  been  made  under  the  same  unusual  conditions;  viz., 
the  same  subject  undertaking  a  similar  feat  of  endurance. 
In  the  account  published  by  Dr.  Pavy  thus  far  I  do  not 
find  any  reference  to  the  results  obtained  by  me  in  1870 
and  published  in  187 1.  If  I  should  not  be  anticipated  by 
Dr.  Pavy,  I  shall  be  interested  to  place  the  figures  of  the 
two  series  of  observations  side  by  side;  but  I  hope  that  Dr. 
Pavy,  who  is  now  fully  prepared  to  criticise  my  results,  will 
give  them  the  study  and  attention  that  he  bestowed  upon 
them  when  he  had  had  no  opportunity  to  personally  test 
their  accuracy.  In  the  calculations  which  I  made  of  the 
quantities  of  nitrogen  of  food  I  used  the  same  estimates 
for  all  the  three  periods,  before,  during  and  after  the  walk. 
If  any  errors  existed  in  these  estimates,  such  errors  would 
have  equal  value  in  the  difTerent  periods  and  would  not 
materially  change  the  comparative  results.  It  would  be 
interesting  to  use  these  same  estimates  in  calculating  the 
nitrogen  of  the  food  taken  while  Weston  was  under  the 
observation  of  Dr.  Pavy. 


EXCRETION   OF   NITROGEN  465 

CORRECTIONS  IN  THE  TABLES  PUBLISHED  IN  187I* 

In  calculating  the  proportion  of  nitrogen  excreted  to 
the  nitrogen  of  food,  I  fell  into  an  error  sufficiently  serious 
to  demand  correction,  although  it  does  not  affect  the 
general  conclusions  deduced  from  my  observations.  I 
first  calculated  the  quantity  of  nitrogen  excreted  for  every 
hundred  parts  of  nitrogen  of  food,  for  each  day,  by  multi- 
plying the  nitrogen  excreted  by  lOO  and  dividing  by  the 
nitrogen  of  food,  which  gave  correct  results;  but  in  calcu- 
lating the  average  proportions  of  nitrogen  excreted  for  the 
five  days  before  the  walk,  five  days  of  the  walk  and  five 
days  after  the  walk,  I  added  for  each  period  the  propor- 
tionate excretion  of  nitrogen  for  the  five  days  and  obtained 
the  average  by  dividing  by  five.  This  was  an  error,  as  I 
was  using  relative  and  not  absolute  quantities.  I  fell  into 
this  error  simply  because  the  process  w^as  a  little  easier 
than  to  divide  the  average  amount  of  nitrogen  excreted  for 
the  five  days  by  the  average  amount  of  nitrogen  ingested 
for  the  same  period. 

*  The  corrections  in  the  tables — which  followed  in  this  article  as  originally 
published — have  been  made  in  Article  XIX.,  as  republished  here. 


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